I kept thinking that Vitiate was the most invincible antagonist and KOTET managed to bring him down (permanently?).. The most likely aftermath here is that the Empire (despite Empress Acina) and the Republic will go to war again.. Although, if the eternal fleet is still under our command, we could stop that..
The only other possibility is that a new enemy from an uncharted space shows up, but again, we still have control of the eternal fleet.. It's hard to have a fleet like threat come up that as long as the eternal fleet still exists.