Nice job with the first two picks guys; I would have taken One Hundred Years of Solitude if it was still available.
I've been going back and forth about several directions to go with this pick. In the end, I'm going to go with Douglas Adams' Hitchhiker's Guide the the Galaxy in the Science Fiction section. It might be a little off-the-draft board early, but I'm fairly confident most of my other favorites will still be available in later rounds. It's too late for me to write much about it tonight, but I'll do so tomorrow.
Now that I have some time to sit down and write out my reasons for picking this book...
For me the brilliance in the book is Adams' ability to be funny on multiple levels at the same time. The humour is in the big concepts: that the answer to life, the universe, and everything is 42, or that a whale can be called into existence a hundred miles above the surface of an alien planet; but the humour is also in the details of the language: in very subtle turns of phrase. Adams' background as a radio writer (and in fact HHG2G's origins as a radio play) really come across with the way the dialog constantly works on clever little twists of language. By the way, the radio series is fantastic, and if you aren't familiar with it, I urge you to check it out; there are a lot of things that made it into the books, but some really funny stuff that didn't.
Also, I love Adams' gift for social commentary; in part because of the humour of the book, he can be very direct in the way that he satires contemporary earthly life with his larger view of the universe. One of the themes that he always comes back to is how there isn't evil in the universe in the way it's often portrayed in most science fiction: there's simply a combination of stupidity and bureaucracy.
Everything in Adams' world is bittersweet: every bad ending has a silver lining, and every good ending has a pang of regret. This is one thing that I think the movie version of HHG2G got profoundly wrong, in ending on a completely high note.