Whenever I toy with a new setting I always go over a few systems to see what fits. Do I create my own? Keep it simple? Use an existing one? Have a look at OGL systems?
However, I always seem to come back to the D6 System, especially for science fiction, as it seems to have everything I need. AntiPaladin Games' Mini Six is a favourite version of mine, mainly because I don't have to write the rules and gamers can get the them free.
I guess that's because I played the WEG D6 Star Wars game from 1987 to the early 2000s, and created a huge campaign setting to adventure in, so the system is properly impressed on me. The system itself is so malleable it can be used for all kinds of things, from high adventure to dark and brooding, and the cinematic feel the rules have give plenty of scope and freedom top the GM. I always loved the Star Wars first edition rules because of their simplicity, and the Rules Companion added a bit of flavour to that. Subsequent editions made changes that I felt uneccessarily complicated things, so I always went back to basics.
I always come back to the D6 System. AntiPaladin Games definitely produced the best version of it, for my tastes.