You got these three angels, that have all served under the similar position as the leader of the Angiris Council at one point in time, or another.
Maltheol, Imperius, and Inarius. They have all served, and they have all done some shady, and just some downright a**hole things to humanity already.
Though, only one of these three actually CREATED sanctuary, as well as the Nephalem.
So, now there are these two dudes left, who actually still exist in some form. You got Imperius, who is a #@@#@**%, and everyone obviously wants to fight him. We also have Inarious, who of which to most people overlook, is that the whole story of Diablo has been revolving around him, and the actions he took a long time ago.
Fast forward to the present. Inarius has been in Hell, being held captive by demons, and has been being tortured for thousands of years inside the Hall of Mirrors. Nobody, has come to save this guy, hes been festering in Hell, for a very long, long time.
Pretty much the gist of what I'm getting at here is, the expansion could potentially have to antagonists. Both of which by the stories standards, should be enemies, and would probably destroy eachother if ever given the chance.
What would this look like?
Well, Inarius would start constructing yet another worldstone in the pits of hell, because the last one he made was destroyed, and he probably wouldn't like that very much. So, Inarius, an angel would actually in a sense become a prime evil. The line between good and evil would be a little grey. Inarius would gain control over hell and its forces, as well as sizable force of angels.
Imperius, hes just a #@@#@**% all the time, so he would obviously wage war against Inarius, even if Inarius does indeed deserve vengeance.
Here we are, mere humans among an eternal conflict, not just waged by demons and angels anymore, but angels against angels.
From there I haven't given much thought. Though I have obviously been pushing for this idea for awhile now. Mainly the idea that Inarius escapes captivity as a deformed monster and causes all sorts of crazy things to happen.
I could of written this a lot better, but you get the gist.