Something that'd really give players something to work toward, while adding a new type of challenge, is unlockable faction variants. In essence, it'd be like adding new major factions and faction traits (Say, for custom factions,) to discover and unlock not by merely winning a game, but by winning it in certain ways, having completed certain questlines, or having conquered and assimilated other minor and major factions.
These variants would in practice, by visual and personality/style adjustments to preexisting major factions in Endless Space 2, playable once unlocked, and potentially always discoverable if random AI results in choosing one. The differences from their original major faction would primarily be visual, ships, leader depiction, and so forth, and in terms of playstyle, would be a tweaked version of the original.


To illuminate and clarify, I will provide what examples may come to mind, and others in this thread should feel encouraged to offer a few suggestions of their own.

A variant of the United Empire, for example, could be unlocked by ending the game in a max-sized alliance, in a game with the maximum number of major factions, and having assimilated a certain number of minor factions. The new variant being some sort of less imperial, more Star Trek-ian Federation-like United Empire, Perhaps having an even more diplomatic/political playstyle than the original, say, a new trait replacing an existing one, that reduces the costs of certain diplomatic agreements by 10-20%. Their affinity could be adjusted to, "Will of the Many," instead of "Will of the Emperor," changing the affinity from +0.1 influence per industry spent, to +0.1 influence per 1 approval over Loyal. End result? A more specialized version of the United Empire. [To vary it further, it could also have an innate trait to be able to trade populations with its allies? Though honestly, I'd like to just see migration treaties become a thing, along with populations automatically tending to move to planets that best fit their needs.]
Many questline results would also be good to base variants on, perhaps. The UE has to choose between Mezari  and Sheredyn cultures (or to merely strengthen their own), and there's also a choice to select an heir. Having one of these heirs take the throne, for example, Petra Manduzik, while having the dominant culture be the Mezari, with their scientific focus, could make for an interesting "Technocratic Empire," variant of the UE.
Same can be said of Hadri Lenko and the Sheredyn, perhaps a new Sheredyn faction outright as a result? Would be a dictatorial version of UE, and a throwback to the original Endless Space.

First example provided, I'm very curious what the dev team thinks of such an idea. Since there's not much replay value once you've seen everything thus far, save for just trying out new strategies, I'm confident this idea would be a big step in the right direction. Easier to slightly modify existing factions, and let us discover/look ip (Let's be honest, people are going to make guides,) how to unlock these cool variations, essentually creating a new game plus for our favorite factions.

Other quick Tl;dr-style summaries of other potential variants:
Unfallen played militaristically, the variant being a thorny, carnivorous plant version of the original. "Snuff out the fire," sort of thing.
Vaulters or Lumeris with a proper focus on piracy and privatering, perhaps?
The "Sated" Cravers, an ecologial version, made up of half craver units and half that minor civ that can reduce depletion. Perhaps with a more isolation and "playing tall," angle, as opposed to the outright war strategy of the original.
Variations based on the merging of two existing factions would be an idea, if a bit more complicated. Hence why it's not the focus of this idea.

All that now said and done, I hope it wasn't too painful a read for anyone. I strongly hope this thing grabs a few by the imagination, and hope that maybe, just maybe, we see something akin to this in the game. I've sank so many hours into it already, and I'm eager to have a reason to sink in even more!