First, a note. At the press we run, we try to give new writers a fair chance. We have even taken stories that needed an awful lot of hand-holding and work to make publishable. So when we decide not to read something past the first few pages, it's not because we're closed-minded. It's because writing decent stories is not as easy as it looks.
With that said, here are the most common problems that put us off of manuscripts at a very early stage. Fix these, and you'll greatly increase your manuscript's chances with any agent or publisher.
1. Content is not what was asked for -- Usually when we call for stories or manuscripts, we're fairly specific about what we're looking for. If a book or story comes in for a specific call and it's not exactly what we've asked for, we won't read it, and your name will go in the back of our minds with a 'can't follow even simple instructions' label.
As an example, in a recent call for cosmic and supernatural horror stories for an anthology, someone sent us a story about how tough immigrants have it. Tragic, and we sympathized very much, but it was nothing we could use. In fact, that story didn't even loosely fit into any category we publish, so it was clear that the author had just seen the word 'submissions', and pressed send. That level of thoughtlessness indicates an unprofessional writer.
So before you submit, make sure that your book is of a genre that the agent or publisher wants to work on. If not, they really won't take it, even if it's superb. Publishing is very niche-driven. Agents and publishers have certain areas of knowledge and expertise, and make contacts that are specific to their market. A science fiction publisher isn't going to publish a historical romance. Books are hard to sell, and a publisher survives, at least in part, by developing a reputation with fans of a certain style or genre. Likewise agents develop certain publishing industry contacts, and know how and where to sell certain genres. So it's a very easy 'no' if you send them anything else, no matter how good.
2. Disastrous formatting -- The first thing anyone will see about your manuscript is the formatting. Even before they read the first word, they'll notice whether it's tidy, whether you have followed standard conventions, whether you have sent them a Word compatible document or something else, whether you've used a readable font. If you haven't done your best to follow the instructions given on their website for how they like their submissions -- or followed fairly standard procedure if there aren't any guidelines -- then chances are your manuscript will not be read.
We've received numerous manuscripts where the writers decided to put sections in a flouncy, nearly-unreadable font in order to show the character was... I'm not really sure what, honestly. Possibly a witch, or an alien, or someone with really weird hand-writing? But the story is not happening on the page. What's written on your pages is the equivalent of the physical piece of film that was fed into a projector to be played on a screen. In this example, the screen is the reader's mind. You don't want your reader focused on the physical strip of film, but on the story playing on the screen.
Basically, you don't want anything about the formatting to distract from the story. If your story requires strange formatting to succeed, an agent or publisher will assume it doesn't actually work. Yes, we know about House of Leaves. HoL didn't need that formatting, it was just as incredible without it, and besides, you're not Mark Danielewski, and even if you are (Hi, Mark!), is this the year 2000? No. No, it isn't.
3. Unpopular content -- There are certain kinds of content that make it less likely your manuscript will be published. Socially-transgressive themes are the main type. Examples of such things at the moment include misogyny, racism and rape. These are just unpopular, and publishers have enough problems already without offending book buyers, 70% of whom are women. There are cases where these elements do make it through, but even when they're plot-critical and handled sympathetically, they still make publishers more reluctant.
A second major class of unpopular content comes from story themes that have been overused in recent times. Vampires, teen dystopias, and zombies became so common for a period of time that readers got bored with them. Publishers immediately stopped publishing books about them. Reader tastes move on constantly, and something new and interestingly different usually comes into sight. If an agent sees that your story is about a now-dead theme, they won't read it. No matter how good it is, it's not going to get picked up.
In general, try to stick to first person or third person viewpoints (and also in general, don't mix the two in the same book). In either voice, the reader gets (at most) the inside of just the viewpoint character's head, and then the things that the viewpoint character can realistically perceive. First person is good for identification and immediacy, but it assumes the viewpoint character came out OK enough to relate their story (i.e. they didn't die or go insane, etc.). Third person is better for introspection, and for building tension, but it slightly less personal. Second person is incredibly difficult to do well -- readers don't really like being told what they're thinking or doing -- and omniscient, well, that's a whole other can of worms.
Many inexperienced writers think it's easier to write an omniscient narrator, one who can see the thoughts and histories of all the characters, and knows everything that happens everywhere. This narrator becomes a separate character in their own right. The trouble then is that the book is this unknown narrator reciting the story to the reader, as if both were in a lounge together with mugs of tea.
But readers get absorbed in a story when they identify with the main character enough to get interested in (and concerned for) the character, and in omniscient, the narrator is the main character. Well, the narrator's not in any danger or pain. In fact they're fine, somewhere comfy, telling the story, and the reader knows nothing about them, not even a name. It makes identification -- and absorption -- very hard indeed, and keeps the characters distant and uninvolving. That makes the text boring.
On top of that, most successful stories are written from the point of view of one single character in any given section, whether in first person or third person. Switch around willy-nilly, and you confuse the reader.
Point of view problems in ostensibly third-person or first-person text may manifest as confusing shifts between different characters from sentence to sentence or paragraph to paragraph. These leave the reader unsure of whose head they are in, and diminish involvement and absorption. But there are also a raft of subtler issues: bits of information the viewpoint character wouldn't know, or things they definitely wouldn't think of at that time, or even when they refer to another person in an inappropriate way. For example, if your character addresses an unfamiliar police officer as "Detective Anderson" in speech, but the character is referred to as "Molly" in description, it'll unsettle your reader.
Occasional subtle point of view issues probably won't get a book rejected, but endemic or major problems certainly will.
5. Summary and Exposition -- Writers are endlessly instructed to "Show, not tell." But this aphorism is almost totally useless as anything other than a reminder. It explains nothing. Isn't all writing telling, given that it's made of words and not pictures? Summary and exposition need to remain limited in fiction. They just aren't engaging.
Summary is a way of quickly conveying events that are necessary to acknowledge, but not interesting enough to write out beat by beat. For example, "The next day, ..." Vital, yes. But only for stuff that isn't important but has to be conveyed. If it's worth writing in summary, always check it's not worth expanding out to actual experience.
Exposition is there to provide information that the characters know, and the reader needs to know but doesn't. Readers are smart, and like figuring things out, so much less is needed than many writers assume. It's common for inexperienced writers to want to explain character histories and descriptions and cool world features, all in great detail. That's understandable -- this stuff takes a lot of time to figure out, and the writer absolutely has to know it all. It's vital. But it's almost all irrelevant to the story. Putting it on the page is like making the reader sit through a four-hour slideshow of your holiday photos. If the characters don't care passionately about it, the reader won't either -- and when the characters do care, it'll come up naturally, without being tediously pointed out.
This holds true whether your information is history or physical description. Very few people pause in the middle of their day to tell themselves what they're wearing, or how old they are, or what color their hair is. If it matters, it'll come up, and if it doesn't come up, it doesn't matter. If it has to be there, remember Graham Linehan's vital maxim, "Exposition is ammunition." If you absolutely have to convey it, turn it into an insult or stinging tease from another character, and make it snappy.
Exposition, extended summaries, and flashbacks (a sub-type of exposition) all kill the pace stone dead. Imagine an action movie where the screen freezes in the middle of a thrilling feat of lethally dangerous acrobatic climbing so that the hero can turn to camera and tell you all about a messy divorce the previous year and how nothing has been quite the same since. It would be disastrous! If you need to delve repeatedly into the past, perhaps you've started your story in the wrong place. A story starts at a particular point for a reason, after all -- because the stuff before it isn't entirely relevant. If you start in media res, in the middle of the action, and then go flashing back to the past, you don't just kill all your initial interest, you annoy the reader on top of it. It's much better, if you absolutely have to add the historical context, to start a bit earlier and write forward.
Moving forwards builds momentum and draws the reader on. Looking backwards drags the reader out of the moment. Think about what it's like when you observe something going on around you. You might look briefly at the wall or the sofa as you pass, but your attention is on what you're doing. The focus of a story is action, and your characters need to think and speak like actual human beings. In a way, a mirror scene is a kindness. Because when your character looks in a mirror and lists their features out -- an act very nearly no real people ever do -- then most agents and publishers will know they don't need to bother reading a word further.
These are certainly not all the issues that will stop an agent or publisher in her tracks, but they are the problems that seem to come up most often. If you can get past these initial hurdles, there are a number of other common issues, but those are more complex, and each one deserves a post of its own.