That is a tough one.
Outside of games based on Intellectual Properties and popular franchises, I usually shy away from 'game settings'. I tend to find the settings RPG companies come up with less interesting than coming up with my own. There are some great ones, don't get me wrong, but they're never as going to be as good as a campaign world I can specifically customize to the interests and preferences of myself and my players.
I suppose that if pressed to choose one and leaving out IP related settings, I'd have to go with classic Traveller. It has space travel, alien species, advanced technology, and all the Science Fiction-y things that I love so much. I also like it's blending of the classic SF literature that I appreciated so much in Junior High and High School - Isaac Asimov,, Larry Niven, Robert Heinlein, Frank Herbert, and many other favorites.
Honestly, including pop culture franchise worlds would be difficult these days as the ones I previously adored have gotten pretty mudded over the past 5-10 years. Too bad there isn't an official The Orville TRPG. If there was, I'd go with that.