I'm not qualified to choose the "Best" SF novel... from the posts here, it looks like that means influential with gobs of social commentary.
But
my favorite and most influential choice is the Hitchhiker's Guide series by Douglas Adams. And I actually reread it much more often than any of the others mentioned in this thread.
So
why is it my best?
- I reread it more often than all other SF books together. IMO, this should be a prime requirement for "good"; a book that has pretentions and commentary, but that you don't enjoy enough to read repeatedly, is not really a good book.
- It has spawned more than any others I can think of - radio shows (okay, they spawned the books), movies, TV show, even a few towels.
- At least in my world (computer science), it is probably the most likely single bit of culture to be known by almost everyone, including many people not born when it came out
- How can you go wrong with "Don't Panic"?