I am an aspiring author. I've often heard that you have to keep your 'target audience' in mind. It makes sense - certain genres attract certain crowds. Well... I want my books to reach as many people as possible. I've heard of books that transcend - or contain - two genres. Snow Falling on Cedars is a good example. Though I have not read it, from what I have heard, it appears to be both a mystery and a romance novel. A book I have in mind has an interesting premise involving time travel. It obviously starts out as a science fiction genre, but could easily delve into historical. Mystery and romance could also be viable genres, based on what happens. The overall genre of the book, however, would likely remain Science Fiction, thus avoiding that dreaded title 'uncategorized.' If I transcended, say, four or five genres, my book would likely attract people of all kinds, right? Or is there a disadvantage to transcending more than two genres?
Even multi-tools generally place significantly more emphasis on one or two of the tools; Swiss Army Knives concentrate on providing a decent pocket knife. Even so, people use them not because any of the tools are as good as a tool dedicated to a specific purpose but because they are convenient and good enough for limited uses. There is a reason for the saying "Jack of all trades and master of none."
If you are targeting airport bookstores, this kind of broad appeal with low risk but low reward may be appropriate. Your readers may pass along the book to others as a broadly entertaining light read, but they will not be particularly interested in re-reading it or talking about it with others.
However, if you want people to get excited about your novel and share their enthusiasm with others, then concentrating on one genre is much more likely to accomplish that goal, especially for a less experienced writer. An inexperienced writer trying to combine multiple genres is much more likely to create a Frankenstein's monster of parts than a complex organic organism. Growing a novel that is true to its DNA will produce rich complexity that the reader will accept as natural and fitting.
Every genre includes expectations and the expectations of different genres can easily conflict. While an attraction to the rational is common in both science fiction and mysteries, it is less common in fantasy. Romance and fantasy are both often set in the past (in terms of technology and culture) and tend to be less focused on realism and more drawn to idealism, but this tends to conflict with the more rational orientation of mysteries. Even the greater departure from realism of fantasy may reduce the enjoyment from the perspective of some lovers of romance, for whom identification with a protagonist (and so some degree of realism) is more important than wonder at the fanciful.
Just as the world and the people in it are complex, so a great novel is unlikely to be so focused on one genre that all other genres are excluded. However, this complexity should flow from the novel's verisimilitude, not from an attempt to cater to the preferences of as many readers as possible. It is true because it is rich; it is rich because it is true.
Being human, authors are complex and will naturally not be satisfied with something that does not richly resonate with their sense of truth. Perhaps the best and simplest advice to a new author is to be human and express this extraordinary humanity in your writing.
You may be surprised at how powerfully a good story can speak to the hearts of those who would not have thought its genre could have any appeal.
It's been my experience that a well-written book that engages an audience reaches many people, regardless of genre.
But one thing to keep in mind. If you plan on writing more than one book, and most of us do, do you want to have to build a new audience each time? And as a new author, it's much harder to sell a book that doesn't "fit" into a category, than it is for an experienced and well-known author.
When I was in school, one of the popular pieces of advice was -- break the rules after you have followed them.
Best of luck!
I will just broaden very great answer by few insights:
You will never make everyone happy There are people who generally hate Shakespeare. And there are best selling books which confuse most of people. The Fifty Shades of Grey is great example of such book (and movie. Yes, they made it into movie).
So, ultimately, focus on telling a story. Although I am sci-fi and fantasy lover, if there is gread story to read, I read it. Example in my case is The Beach which is totally out of my normal area of interest, but I loved the book totally.
Crossing genres too much can be overkill: Yes, I bought recently a movie which got translated to my language as Attack of Nazi zombies because I was really really curious, how bad the movie can be. (It was so bad, that I did throw it out half an hour in).
If you have idea for a story where Mr Spock and Luke Skywalker got warped to nazi Germany and fight nazi zombies using fantasy spells (and then they fall in love to each other), try to write it down. But, if you cross genres too much, the outcome story will be mostly "just plain stupid"
And last but not least: Good examples of things which cross genres:
Genres like Science Fiction, Fantasy, and Historical Fiction are mostly defined by their setting rather than the type of story. Thinking of Orson Scott Card's MICE Quotient... Within any of those settings, you will find many stories that are primarily about Milieu (exploration, travel), Idea (mystery, problem-solving), Character, and Event (disaster, war). They can also include elements of horror, romance, etc.
I don't think combining a setting with a story type creates the same sort of problems as doing a mash-up - like a Jane Austen zombie novel. If your book could interest two different groups of readers equally, i.e. SF and Romance, you can market to both groups, though if the SF setting is mostly window-dressing, for example, I'd concentrate most of my efforts on romance readers.
You say you want your books to reach as many people as possible.
In my writing, I focus on a very specific audience: people who are technologists or love technology and who think about the future. When I focus this specifically, I'm always going to alienate some people who fall outside my target audience. But on the other hand, the audience I'm writing for is going to love my books even more deeply, and recommend them to friends.
The world is an enormous place, with over 3 billion literate people, and about 330 million of those native English speakers. If a book appeals to one percent of people, that's 3.3 million people who would enjoy it in English, and 30 million in all languages.
Now look at the bestselling books of all time on Wikipedia. They have sold in the 10s of millions. A book that appeals to just 1% of the population could become the bestselling book of all time.
A book that a few people will love will probably do better than a book that many people may like a little. Those few who love it will spread word-of-mouth far better.