I don't know if it counts as science fiction, but my favorite genre book of all time is Guy Gavriel Kay's Lions of Al-Rassan. I hesitate to call it fantasy because there is no magic and it does happen on another planet, but the story also feels like historical fiction because it's basically a re-imagining of the Legend of El-Cid.
A close second would have to be Gate to Women's Country by Sheri S Tepper, which is near and dear to my heart as it was my first foray into hard-core science-fiction. Up until then, the Wrinkle in Time series was the closest I got to sci-fi, but in freshman year of high school, we had to read it for English class, and thus I was introduced to the Sci-Fi/Fantasy section of the bookstore. Ender's Game, Dune, Hitchhiker's Guide to the Galaxy, and Star Wars and Star Trek soon followed, but it wouldn't have happened if not for that first one.