Depends on what you want, but I liked:
Fading Suns - think a modge-podged medieval Europe in space. It suffers some from trying to be too close a mapping of medieval Europe ("here's the Space Vikings, and here's the Space Muslims, and here's the Space Catholic Church"), and it wants to be a game with a strong religious presence but never defines what that religion does and doesn't believe in, it wallows in 90's era White Wolf stereotypes at times (fitting since it has some of the same writers... and it dabbles with wanting a more operatic "good vs bad" vibe at times, before recanting), and the system kinda' blows. But it's also one of those great settings that allows for dang near anything you'd want to add to it while providing a perfectly solid setting without making GMs add stuff, there's a whole secondary game devoted to miniature space ship battles in the setting that is portable into the RPG (it even has detailed ship maps if you can find them (good luck!)), and it manages to riff off of Dune and Warhammer 40,000 while still feeling like its own critter.
Rogue Trader - the RPG by FFG. You and the other players are the command crew of a city-sized space ship in the Warhammer 40k universe. Mechanically it's as big and ugly as the ship you'll command, but the W40k universe is another setting that allows for a wide range of stuff. And the default campaign is "go out and exploit the galaxy in the name of the Emperor and personal profit. Here's a small army and your city buster of a starship." Star Trek this aint. There's also other games covering said small army, super soldiers better than said said army, the holy Inquisitors who root out enemies of the empire, and a whole game line devoted to one of said enemies (you want to play demon worshippers from Hell in outer space? Black Crusade has you covered.). The books are riddled with editing errors, the mechanics are cumbersome, and still you can only try to pry these books out of my cold dead hands.
Rifts Phase World - Palladium was doing OSR gaming before OSR was cool. Palladium still isn't cool though. But Phase World kind of is. Set on a multi-dimensional nexus point that also doubles as the nexus for three galaxies (because one galaxy is clearly too small for Rifts players!), this game has marketplaces run by evil cosmic gods, super hero space knights flying around at FTL speeds, ancient aliens bending reality, deal with the United Worlds of Warlock (you want fleets of dwarven spaceships? Because this is how you get fleets of dwarven space ships!), and lots and lots more! Plus, it's compatible with all the other dozens of Rifts books out there (more or less). So unleash your inner munchkin, laugh at the incomplete ruleset for character creation in the main Rifts rulebook (you'll need it to use Phase World), and then realize it's all straight faced and serious. Mostly.
Blue Planet (and Polaris) - Because you don't want a whole galaxy so much as a detailed alien ocean-themed world. I'll admit it, I only got this because I wanted a ocean-world to use in the above games, and was looking for something to read. Polaris is... basically the same thing, but more technologically advanced and with different mysteries. It also is set on the ocean floor, whereas Blue Planet is set on the ocean's surface and near shore. Also, there's systems if you care. I didn't. A good choice set if you're looking for some harder sci-fi though, or something you could port into another setting with minimal to no effort.
Fragged Empires - In the far future, humanity is dead and the galaxy is populated by the races it created to take its place. They try to play with each other, but... it's hard. Especially since some of them are genocidal machines, while others are just plain hungry all the time. I like this one just for the ideas it generates, as the system itself tries to do a lot of admirable stuff, but in the most oddly worded and haughty presentation I've seen since the 90's. Still, it's a fun read and walks a good line between soft and hard sci-fi I'd say.