I think it's unlikely the Enclave will return as a major antagonist, not in a game set after 2277, anyway. And they weren't absent in 76, their members were dead at the beginning of the game just like all other human NPCs.

My personal headcanon is that after the NCR's victory at hoover dam, with both Caesar and Lanius dead, the Legion breaks up with the various centurions becoming reigonal warlords, until some enclave remnants (officers/colonel) start reuniting the legion using their hatred of the NCR and slightly twisting the legion's beliefs by claiming Mars sent them with new weapons (enclave Power armour and plasma weapons) to take revenge on the NCR.

In my mind the Enclave returning as a puppet master for a larger faction makes the most sense. As has been stated, by the time of fallout 4 the enclave has gone underground, relying on subterfuge and stealth rather than their previous "kick-down-the-door" approach (see frank horrigan). So in order to gain any control over the wasteland they would have to do it through someone else. And a post NCR-victory Legion would have the right motivation to become pawns of the Enclave. (and enough stupidity to do so without realising)

Although I wouldn't mind it, seeing the Enclave re-emerge again as a major force isn't something I am thrilled for. Perhaps in a minor way, yet we have seen them fail and subsequently destroyed multiple times. As the Wasteland is an enormous plane, I would prefer to see new antagonistic factions come into the fold.

^Yeah it's at that point where any attempts to reintroduce the Enclave are going to need really good writing. At this point as far as we know almost the entire west coast Enclave fled to Raven Rock under the command of Eden after Fallout 2, and were destroyed in Fallout 3. Assuming they're moving forward from 2287, unless it's a group like the Remnants, who disobeyed the order to retreat east, its going to have to be a entirely new Enclave contingent, and then they'll have to come up with a reason why they weren't at Raven Rock in 2277.

Maybe if some Enclave remnants discovered synths, they could try to reverse engineer their teleportation parts and infiltrate the Institute. Then, they could make some sort of alliance that eventually either becomes the dominant power or collapses into civil war. Just spit balling, so to speak.

Alternatively, maybe some of those South American groups could form a sort of coalition and start encroaching on NCR territory as a preemptive strike of sorts.

I just want to be able to side with the Enclave

This is not a thought I’ve developed well yet, but what if Vault-tec re-emerged and starts trying to take back crontrol of any functioning Vaults or Vault dwellers? I think a surviving group of Vault-tec execs could be a decent antagonistic group, though the result might just seem like a rehash of the Enclave and the Institute.

No more Enclave. New Faction to move the story further and expand the world, for god sakes we already have too much BoS.

Maybe a couple more references to the enclave and maybe some actual npcs in the white springs bunker.

but yeah some mega faction couldn’t really be around

What about a secret enclave presence in Canada?