While the Enclave is a generally cool faction, with black power armor and energy weapons I really don't think they will (or should) be in the next game. From a game developing standpoint they've been used as the antagonist in both Fallout 2 and Fallout 3 and are 'destroyed' twice. While it does make sense that they are still around in lore, as pointed out by ED-E's dialog hinting that there might be a secret base in Chicago but in actual practice to put the Enclave into the next main game or spinoff would be a overused antagonist and awfully boring. I think the developers realized this, and gave the Enclave a tribute at the end of New Vegas. But I guess times moved on for our friendly neighborhood genocidal American government remnants.

Man i've been thinking and sighing the same thing at idiots that really believe that the Enclave should return as a main antagonist, they were literally blown up in 2 and Beth recycled them in 3, it's just ridiculous and lore breaking the idea of a comeback. I agree with all you have said. though if not a "big comeback" it'll be really cool to see them as a minor(little, tiny, miserable) faction trying hardly to regain power in their respective location(for obvious reasons)( also that the appearance should be make sense according with the game, location and plot, that if they have quests or have something to do with the main storyline), or maybe just some remnants(like in new vegas, but obviously implemented differently)

Hmmm, Yeah the Enclave shouldn't return, hell we got the evil BOS Bethesda gave us, but i think it would be logical and fun to have a remnant group of the enclave in the next game that will give side quests.

I agree, time for a new big bad. There is a big country out there and it would be more exciting to go up against someone other than the Enclave.
I mean you would have to think there would be someone like Asher from the Pitt. Someone with a Army and is a threat. Maybe a Raider boss who could unite the raiders into a single army who wants to take over a territory and it's up to a hero to prevent it.

Well yeah, its perfectly reasonable to have Enclave remnants like they did in New Vegas, but from a story line having the Enclave as the antagonist again would be a bit too much.

@Katzenfleisch of course, you know i would really like that in the next fallout game maybe the main clash would be between the NCR and the BOS, i mean they have been so build up in the past games as being getting stronger in each one, so i guess that clash would be unavoidable, of course taking in to consideration that the BOS in 4 and the NCR in NV are canon, but even if the one in 4 isnt canon still the BOS got strong after defeating the enclave in fo3