I think the prophet is going to be more along the lines of Malthael then Inarius. For one, I got the impression the Enchantress is from after the Sin War (and Inarius has been in Hell since then). For two, it just wouldn't have been his style, from what we saw in the Sin War Trilogy (you know, aside from the name "Prophet").
The writing for Diablo III was pathetic, but if the black soulstone just "happened to go overlooked as it was kicked through the gutters of heaven by many a sandal-clad foot," that would be the biggest load of horseshit known to writing. That's like a preemptive deus ex machina coupled with a spell of multi-dimensional global amnesia.
I took it as when Diablo died, he fell off the spire, and they weren't able to retrieve the BS. Also, it's been pretty clear that the Angels aren't exactly genre savy, I think it's pretty consistent if they think the threat is over, at least for now.
At least one of the expansions should center around Imperius going rogue and waging a war of extermination on anyone with the slightest hint of Nephilim blood. Your character could travel to the origin places of all the characters from D2 and D3, both protecting and avenging those who would fall within harm's way. Imperius could use his powers to summon other creatures of heaven, but twisted to his own ends. It would be like starting the game series over with heaven as the enemy and no convoluted and implausible retconning.
I really hope it's not primarily about Imperius. I feel he's boring and one dimensional. Also, we already clobbered Diablo, who clobbered Inarius (twice). It'd be a bit of a stretch to say that he's actually tougher to beat then Diablo (united with the other evils).
I think we have more than enough with closing up the Templar's, Scoundrel's, and Shen's story lines, not to mention what they've already said about Adria. And Maltheal.
That said, I wouldn't mind if we do fight Imperius, but he ends up being a mini-boss for Adria/Lillith/whomever ends up being the big bad(s) of the expansion.
And to whoever was talking about Andariel/Duriel still being around, they aren't. They got pulled into the soulstone along with Baal, Diablo, and Mephisto. Otherwise Diablo wouldn't have been THE prime evil, cause he'd have been missing those two.
Regarding expansions, I'm not sure if this was brought up, but in the Collector's Edition interviews with the game developers, they did say this (paraphrased):
They do want to explore the salvation of Leah's soul after she becomes Diablo and her body is essentially destroyed at the end of the game, simply because it feels like the right thing to do from a traditional storytelling stance.
I'm convinced the 'prophet' we hear our Enchantress speak of is Maltheal, not Inarius. Tathamet won't be seen as his destruction along with Anu's is what created the Burning Hells and the High Heavens respectively.
All signs point to the expansion(s) dealing with the whereabouts of the Black Soulstone, the pursuit of Adria, the corruption of Imperius and the restoration of Leah's soul.