Civilization: Total War. IN SPAAAAAACE!
You are a Rogue Trader given the task to explore, conquest and colonize a section of space. You got your fleet, initial resources and a colony. You move through the sector, revealing systems and planets, discovering aliens and dangers, etc. Colonized worlds produce resources for you and grant you bonuses. You can also discover different things, like technology, lost colonies, relics, etc.
There are different factions that need something for you and different allegiances affect your game. Admech will want tech and control over production, Ecclesiarchy shrine worlds, relics, and faith, Munitorum will demand fighting men from the colonies and weapons, etc. You might discover a Maiden World that you can either colonize and make a mortal enemy out of the Eldar while bagging a fine world, or let them be and get people riding our ass about "Why haven't your purged dem xenos yet?" From time to time a crusade might be launched and your loyalty is measured with the resources you put into it.
If you're really good, the High Lords might put a new Marine chapter within your sector, which means you'll have some good friends on your side, as long as they're cool with everything you do and not some pious assholes or total murder freaks.
You also need to have heirs and shit, or you death from old age or an assassin will end the game. Also not meeting the set requirements of your charter, it can be revoked.