I strongly recommend Galactic Civilizations II and its expansion packs, by Stardock. It's basically Civ 4 set in space and with planets instead of cities. There's a gigantic tech tree, with multiple paths just like in Civ 4, and you can (and are encouraged to) create your own units using a Spore-esque ship builder. The game is way too deep to describe here, with political parties, karma options, and huge amounts of customization before the game. If you liked Civ 4, then you'll love this game!
