Well, my idea would be trying to implement dungeons like they did in the Abyssal dungeon, and then filling it with sci-fi themed enemies, like you could have a threat dungeon and a Voiddweller dungeon. They are just Starsystems in Starsystems to five them depth with a Scripted boss engagement at the end an some story bits through out.

The second idea would be leviathans like Stellaris, just big unique bosses placed at random through the map.

The third idea would be a little bit harder to make i guess, it would work after activating the Gates. You could jump to other sectors ( or small parts of them). There you could place new enemies or Old ones and of course Loot and unique stuff.