Depends on how much of a change you're looking for, really - just the genre, or mechanical change, too (though I'd say most sci-fi games are mechanically different from d20/D&D). Also, what are you looking for in a game, other than "sci-fi"? Those answers will help narrow down suggestions.
Star Wars: you're looking at a game that is (depending on the version) either out of print, or soon to be. There's the old West End Games d6 editions (out-of-print), the initial WotC d20 offering and its revised rules (out-of-print), and the newest d20 Saga Edition (soon to be out-of-print). The Saga Edition rules are, I think, the strongest offering from WotC, but others can go into better description of its flavor.
FATE-based games: Starblazer Adventures (more space opera) and Diaspora (harder sci-fi). FATE rules are pretty different from D&D. VSCA has the Diaspora SRD on their page, so you can peruse. If I were to run a straight sci-fi game right now, I'd probably use Diaspora.
Other games I'm not familiar with, so I'll let someone else pitch them :P