I prefer my sci-fi to be about some scientific breakthrough and the consequences of that breakthrough(main reason i never really cared for Star Wars).
Alpha centauri: Aside from the main plot, the rest is fantastic and one of the most believable settings in a game, it also makes you really feel like you are taking a civilization into the future.
Deus ex: should be obvious why.
Mass Effect: would be amazing if there was a way to remove Shepard, the Starchild and his gooey reapers in addition to mechaSaren/illusive man (and probably also the Asari) from it .
Checking out seems not to do much.