The weird thing is, if you think about it, despite that lore for the Eternal Conflict, it actually hasn't been relevant to us fighting Diablo. Prior to Diablo 1, he was trapped in a Soulstone, and used his influence to convince Lazarus to free him. In Diablo 2, the hero of the first game failed to contain Diablo's power once again and became Diablo's host. The entire point of destroying the Soulstone in Diablo 2 was to destroy Diablo forever, banishing him to a realm he couldn't return from. He's only back in Diablo 3 because they invented the Black Soulstone which apparently intercepted the souls of the Prime Evils on their way to being banished.
Frankly, it kinda annoys me. There is no shame in an artifact title. The Diablo games can be fun without Diablo himself appearing in them. Diablo 2 ended with the main three gone for good, but Sanctuary was about to change forever thanks to losing the protection of the Worldstone. Diablo 3 retconned the nature of the Worldstone and retconned in the Black Soulstone in order to more or less retread old ground. I think the barriers between realms being shattered would have felt more than enough like a Diablo game without Diablo himself. If the story doesn't move on from that, there'll be nothing to be invested in because we've seen it before.
As for the ending of Reaper of Souls, the other evils have not been released, it's just the super Diablo still:
http://www.diablofans.com/news/48075...tream-gamblingAfter the death of Malthael, the combined Prime Evil Diablo was released, rather than the individual Evils.
I've speculated on where the story might go next, but I'm really not sure. I doubt we'd just go right back after Diablo, even though that would be a pretty logical action to take, because it would feel redundant. Diablo 3's story is definitely of the Nephalem though, in both the base game and the expansion, and I think a second expansion, at least, would continue that. In the base game, we discovered our nature as Nephalem and came into our power, and in Reaper of Souls, even the angels came to realize the implications of that power. While they were too busy worrying about Diablo and Malthael before, the player now has the attention of both Heaven and Hell, and I think the Nephalem will now take center stage. Inarius and Lilith definitely seem like potential candidates to appear, considering their connection to the Nephalem, but I can't say in what capacity.
If I had to make a guess, I'd say that the events of Diablo 3, and especially Malthael's mass extinction, will have awakened the powers of many other Nephalem out there, and they're going to be very upset. The villain might end up being a new Nephalem who kills the angels and demons equally. I could also see Imperius being his most sympathetic at a time when he's openly after us, even if it's still misguided, because the Nephalem are truly threatening the angels.