I've been involved in two RPG campaigns. One was some time ago and used the FASA system, which I liked. We tweaked the core rules for character generation and ship design a little bit though to suit our own perceptions of things and because we wanted to play a game set in 2282 to begin with. Some of the later supplements dealth with this period. It kept us going happily for about three years.
The second campaign was set beginning in 2376 and we used the Decipher System. At first I found the character generation system awkward because of the way the sections were arranged in the books. One had to keep flipping back and forth to move from one part of process to the next and in some cases had to refer to things in different volumes. I found a handy character generation guide online that helped with this. Now the process seems fairly easy. I found the ship design system easy to use, but also found that for my taste it tended to produce "cookie cutter" classes. I handled that by once again tweaking the system to give it a bit more variety and flexibility. The mechanics of the battle system seemed good to me, although a bit complicated when one wanted speed of resolution. Still they give a good feel for maneuvers that read like they're right out of a script. Our group tends to go for narrative effect over number crunching though, so we tend to roll dice minimally and let the narrator move the action along according to his or her sense of dramatic pace.