I definitely second Blue Planet. The system is stupid-easy, and it's one of the best and most realistically extrapolated settings around, period. One of the caveats of the game is that life isn't fair, and all men are not created equally, so it requires mature players and a strong GM's guiding hand, especially during character creation. Otherwise you could end up with a bunch of ex-shocktrooper mercenaries with nothing to lose and bigger guns than everyone else. If you read the book, you'll know what I mean.
If you're looking for something generic, I'd recommend Alternity. It's out of print (and has been for quite a while now) but it's well worth it if you can find a copy. Both of the published campain settings are worth a look, as well. The DarkMatter setting is about weird conspiracies and aliens and what-have-you. It really raised the bar with regards to what's expected of a gaming resource (at least, it did for me). The other, StarDrive, is far-future space opera, so you have star-spanning nations, alien invaders, and space fleets. The stuff dreams are made of.
If you don't mind waving your geek around in public, there's always Decipher's Star Trek RPG. It's the same engine as their Lord of the Rings RPG, but toned down and cleaned up. Plus, phasers can do "kill" for damage. No dice rolling. Rather neat, that. Speeds up gameplay quite a bit.
And finally, if you're not afraid of the big bad (White) Wolf, there's Trinity. Now, the main book is a little dull, but the expansions really flesh it out. Very similar to Blue Planet in that it's a very plausible (given the assumptions of the setting), well reasoned-out setting. It almost qualifies as "real" sci-fi in my book, but the super-powered monsters and the weird mind powers leave me a bit cold. However, I hear it's going to be d20, so it may get a good polishing.