I know a couple of writers who, offered a two-book contract on the basis of their first novel, turned it down on the grounds that the book they wanted to write next wasn't remotely like this one, and they didn't want to be tied into a contract that was expecting it to be aimed at the same sort of readers. (There are other more businessy reasons for turning down a two-book deal, but that's for another day and probably another blogger.) And if you get in among any gathering of literary-ish writers, much of the grumbling is about how publishers only want authors to write the same book all over again.
I do sympathise with the feeling; all three books in my personal TBW (=To Be Written) queue will seem perfectly reasonable to people who like the ones they've already read, but I do reserve the right to write a peculiar techno-thriller if I feel like it, and if anyone actually said to me, "You know that you'll have to write The Mathematics of Love forever, now?" I'd probably take up market gardening. And the chit-chat among aspiring writers about whether you're "allowed" to put X in chicklit, or "ought" do Y in fantasy, always makes me seethe: who is it who has the power to allow or disallow what you want to write? Who says "ought"? And do you really think you'll sell the book if you just tick the right boxes and none of the wrong ones?
But if you stop thinking of publishers (or the capitalist system) as bean-counters hell-bent on crushing literature, and understand the nature of people and books, it begins to make sense. Fundamentally, the book trade is always trying to sell something which people have to buy before they can try. (Hence the importance of covers, blurbs, puffs, prizes, editorial coverage, reviews and so on, and, of course, a writer's name). And on the whole, people want value for money and for their time. They want to be confident that if they spend the time and the money the book will deliver what they're looking for: in the broadest sense, they want pleasure. That pleasure may be that the murderer (or the husband) will be caught, or that they'll laugh their socks off, or they'll live and breathe Taliban-controlled Afghanistan or Goth-invaded Rome, or that they'll be surprised by a completely new vision of their home town or their grandparents' generation. It may just be that they'll read writing which makes humdrum life for a week afterwards seem extra-vivid and slightly off-kilter. They want one (or more) of those, but a human has to know what something is - it has to be familiar to that degree - before they can want it. So, with relentless logic, I would argue that any book that readers enjoy will offer them a familiar pleasure, and the whole book-trade is geared to trying to explain what that pleasure will be.
So, never mind what you're burning to write, or what's never been done before, or what will sell. That's all stuff for your journal. Instead, ask yourself this: what familiar pleasures are you, in all your writerly uniqueness, offering your readers?