Well, it's a 2012 interview.
With info we have now it's pretty easy what Metzen was talking about
: the storyline. Basically he said that the grand plan Diablo was all about was to be able to invade the Heavens, which he's been able to thanks to the intervention of the nephalem multiple times (the first reincarnation, the warrior not destroying his soulstone and the destruction of the worldstone to name a few).
Anyway even after all the crap we have put up we have been able to stop his plan - this is the end Metzen talks about, also very clearly now.
What we have left:
- the black soulstone is still around with the souls of Diablo and all the lesser evils we killed
- Malthael story arc which pretty much states nephalem are not all good and corrupt by the source
These two alone could make for great storylines. Not counting the other greater evils, and the fact that angels can see us as enemies as Malthael did. Plus the Sanctualy world is way bigger that the regions we have seen, hence new zones can pop up and have their own lore made.
I don't see the Diablo franchise much dead. More like going for another expansion after RoS and then again 12 years for chapter 4