I'm never able to narrow down to just one, so I'll list those that have been at the top of my list for a while, and a few others I've just recently started digging:
A Scanner Darkly by Philip K. Dick: I just love this book. It's a little more grounded than his other novels, and just so much more meaningful when you realize it's inspired by his life and the deaths of several of his friends. And being a Dick novel, it's full of the usual head-trippy questions on reality and morality that have no easy answers.
Warchild by Karin Lowachee: I will never get tired of this book. I can read it over and over (I've read it at least a dozen times already) and I always find some little nuance I missed before. Anyone who doesn't believe SF can be character-driven needs to read this. The characters are subtle, their emotions powerful, and the universe incredibly well-realized. Love it.
An Exchange of Hostages by Susan R. Matthews: Like the book above, this one can be uncomfortable at time, but in a good way. Any good book should make you squirm a little bit. *grins* This one features a protagonist who, try as he might, can't entirely step out of the anti-hero mold. He desperately wants to be a good guy, but...that just won't happen. Not entirely. And the setting is one of the bleakest, yet most interesting universes I've lost myself in. Fantastic, and a fairly recent discovery for me.
Dragon's Winter by Elizabeth A. Lynn: This book reads like poetry. It's fantasy at its best, of the type I just don't see much of anymore. And if the giant stamp of approval from George R.R. Martin on the cover doesn't get your attention, the opening page damn will. The writing is just beautiful, with a lyrical quality most can only dream of. And the story itself is very poignant and emotional. Great book that few people have heard of.
Catch-22 by Joseph Heller: I loved this book the moment I started reading it in English class my senior year, and I love it still today. What a wry, jovial tone to stand in utter contrast to the horrific time and setting. I just love the juxtaposition almost as much as I love the characters.
Revelation Space by Alastair Reynolds: I just read this one off of someone's recommendation. Sure, some bits are a little out of my depth, but Reynolds really makes the science accessible even to those of us who aren't professional physicists. And the plot is very intriguing, with a tangled cast of characters all offering a unique viewpoint on the world. As with almost all the books on this list, there's no easy good/evil divide. That just makes it more believable and infinitely more interesting.