I suppose the book I've read the most times would be Hemingway's The Sun Also Rises, but not since I wrote a thesis on it almost four years ago. Just more proof that academia is indeed the death if passions, I suppose.
The genre work I return to the most often these days would be R. Scott Bakker's Prince of Nothing series. To me, it is the perfect symbiosis of high prose, philosophy & insight, and profoundly well-crafted characters and setting. From the perspective of an old literature & philosophy student, it is easily the most accomplished modern work of fantasy.
I see many of you also mention works of philosophy that have affected you more than most, and while I personally rarely return to a work of philosophy after I've worked through it as it were, I'd still mention René Guénon's Crisis on the Modern World. It truly opened my eyes to a broader spectrum of cultural awareness, and actually kinda helped me put my own life in context. It's not as intellectually stimulating as Wittgenstein, nor as funny as Nietzsche, it's a little pompous, yet still very rewarding.