(Pure speculation)
Throughout the Diablo games we learn what fate befell the heroes from the previous installments; however, in D4 we’ve been told that Heaven has “shut its doors”, the prime evils are returning, and Lilith is already back. So, where are the nephalem, who are arguably the most powerful heroes/beings the world has seen in a very long time? Hand waving their deaths would seem really cheap, and while I could see some falling to corruption, I think it would be really good to see them as pillars of the world trying to keep it afloat. Did we uncover anything from the demo at BlizzCon, or out of any books?
On top of those thoughts, there are several heroes from D2 that remain unaccounted for, and whose stories need resolution in either D3 or 4.
Keep in mind that some time has passed between D3 and D4, so not all characters will be relevant, or even alive, in the upcoming game. Even less so with characters from D2, of course.
I have a theory that it is in fact the now-overpowered, and possibly corrupted, Nephalem of D3 (or their descendants) that are who the Triune are summoning Lilith to help defeat. The question then is where we as player characters stand in this conflict …
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I really hope our D3 heroes don’t “fall to corruption” I find that trope rather… disappointing.
I agree that just saying “they died” would be cheap as well.
However, they said this game is set “decades” after the events of Diablo 3, perhaps they could mean so long that the D3 nephalem died of old age? though that could be just as cheap, however it would be the easiest way to get the “more grounded” story they say they want for D4, our D3 characters are absolute units, powerhouses of near ridiculous levels, what could’ve possibly challenged us after we killed the prime evil and death itself?
My only thoughts along that line would be a faction of “evil” nephalem that start making moves, and our good nephalem from D3 are on our side helping to fight back against them.
Honestly I would actually really like it if they came back as a part of the playable character roster, perhaps even some of the D2 heroes could come back as part of that roster too!
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The previous episodes let us know that things are going from bad to worst. With all the little details coming from other Blizzard games and short stories it seems that the Barbarian and the Amazon have escaped both, death and corruption.
In the coming episode, Diablo 4, there’s surely going to have enough options to customize an old character, maybe a very old one 
(if some players have a story for their character, after all t’s an RPG)
Personally, I didn’t like the naphelem thing in D3, because first of all it was bad enough to make me skip all the cut scene… too bad I couldn’t skip many dialogue. What I do appreciate is the fact that no matter what the 7 Evils always do a step forward and their defeats hide a guaranteed victory, at least this is what the state of Sanctuary in D4 seem to show.
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If Mephisto is in Diablo 4 than it would be ironic if the Crusader becomes Mephisto’s new host. 