Alien Invasion in the storyline.

[DoubleNwah]

I know this is utterly ludicrous and highly unlikely to happen but I think that a really neat end game enemy that tries to stop you rebuilding the commonwealth could be Zeta aliens. In the lore it's almost entirely confirmed that the aliens started the great war to get mankind from developing and becoming a threat. So maybe once you build up a very strong and advanced civilization at the end game the aliens could invade to try to stop humanity from being a threat. Because honestly the gunners just aren't that compelling of a Villain after I single handily raided gunners plaza and killed their leadership.

Maybe you'd have to build a lot of those huge cannons in the defensive plots to down Zetan spaceships or something.

 

[Vrond Winterwolf]

I always felt the war was started by Vault Tech. A possible answer for where Vault tech went is the worked with the Zetans to make an off world base for Vault Tech and in exchange helped the Zetan's start the war. As for new factions one solution is make them like a DLC that triggers after the events of the Vanilla game. The large end if game explosion gets the attention of the new faction.