I haven't played all the games on this list; some of them haven't been released yet.
I love sci-fi most when it introduces me to a concept or technology unlike anything I've previously seen. I included a few games that barely fit my definition of a sci-fi game (You don't really see anything in Mirror's Edge that couldn't happen in the present), but I tried to exclude fantasy and surrealist games (The first Myst, The Witcher). Basically, my current definition of sci-fi seems to be that there is advanced technology and/or aliens. Not sure if that's a good definition, but I'll edit this list if/when I think of a better one.