It’s a 3D first person game instead of a 2D isometric, and most of the differences stem from that. More manual building (they added blueprints but I don’t know how good they are), infinite resource sources which means setting up a mining outpost is permanent. Much less focus on fighting wildlife, though that is present.
Overall, it’s a much more relaxing, slower paced game than Factorio. Both are good at different aspects of the same thing.
There are several good total conversions for Sins of a Solar Empire: Rebellion. Star Trek Armada 3 is the most complete overhaul I’ve played for it. I’m a big fan of Halo spaceships and the Sins of the Prophets mod is the closest thing I’ve seen capture the asynchronous battle between UNSC and Covenant ships. There are others for Star Wars and Stargate that I hear are good, but I have not tried them.