Nephalem Valor. Nephalem this. Nephalem that. All anyone ever seems to call me is Nephalem. My character seems to know what it means, as evidenced by her suspicion that she could not gain entrance to that sunken temple in Act I, which only Nephalem are supposed to be allowed into. I seem to recall a remark that 'all of the Nephalem were dead'.
And yet… I got into the temple. And everyone – I mean everyone in the Hells and the Heavens calls me Nephalem. So fine. I give up. I'm a Nephalem I guess. But, well, what the hell is a Nephalem anyway?
Best Answer
Nephalem are the children of mixed parentage - angels and demons who created and fled to Sanctuary to avoid the perpetual war between heaven and hell. "Sanctuary" is the primary place where the Diablo games take place, and all of the humans are descendants of these first Nephalem. True nephalem are able to tap into their supernatural powers. Not every "human" in Sanctuary can tap his or her supernatural powers, but the heroes in the Diablo series can.
The paper manual that comes with the boxed copy of the game has a bit of backstory/explanation:
(it's continued on another page, but it's unrelated to the current question.)
Tyrael explains this to you, if you ask him about "The Creation of the World" during Act 3, Machines of War:
Some additional lore is available in act 4.
Auriel also explains this in a 4-part lore series titled "The Creation of Sanctuary"
Itherael mentions the Nephalim in "The Destiny of the Nephalim"