So I have some, not really predictions, but musings on the direction the series could possibly take.
First of all, I'm going to referring back to the prophecy:
So, the first thing I note is that several of the lines were not in any way metaphorical. Wisdom shall be lost as Justice falls literally happened. Maltheal disappeared and Tyreal fell to Sanctuary. And then, Hope was swallowed by Despair.Wisdom shall be lost as Justice falls upon the world of men. Valor shall turn to wrath - and all Hope will be swallowed by Despair. Death at last, shall spread its wings over all as Fate lies shattered forever.
So I'll be looking at the other two lines.
Valor shall turn to wrath. So yeah, Imperius is an angry bastard, but I think there's a deeper meaning to the line. I think that Imperius is literally Wrath, as in one of Azmodan's Sin lieutenants. I can totally see Imperius being so hellbent (ha!) on defeating Diablo that he's teamed up with one of the other Evils. In that light, the animated Diablo: Wrath trailer has deeper meaning. Combined with the mention of the Lord of Greed in the lore for the treasure goblins, and I can definitely see an upcoming expansion focusing on Azmodan's remaining sin demons attempting to take control of his army and start the war anew. In fact, I could see Imperius leading them as the would be new leader of the Burning Hells in addition to his post as the leader of the High Heavens.
Secondly, the line "Death at last shall spread its wings over all as Fate lies shattered forever." Well, to me this says that the Angel of Fate is going to get broken, while Death, possibly also an angel (Inarius, anyone?) will rise to prominence. Additionally, there are enemies in the game known as the Heralds of Pestilence. Their story is that they were demons who rebelled against Azmodan and were punished. But their name implies the existence of a Lord of Pestilence. Combine this with the mentions of Death in the prophecy and I could a new faction in the Eternal Conflict being Sanctuary's version of the Four Horsemen.
Anyway, that's just my two cents. Thoughts or comments anyone?