Third person could work, look at Kingdom of Amalur. I'd personally prefer the option of being able to do both a third person or a fixed isometric angle at will. To make the 3rd person work would probably require some nice dodge movement, which is something Diablo could use. Given the Diablo games have a closed quarters feel, 3rd person shouldn't provide too much of an advantage to the other angle, or include the "fog of war" that Warcraft 3 had with light resonance returning to the series for larger areas. Also a dodge non-skill move would be great seeing as to how Diablo 3 heavily relies on movement skills like teleport and vault. Even playing D2 now, dodging feels cheap and slow. The dodge in the consoles of D3 isn't worth using, so nobody uses it (unless dodging still works with frozen).
However, the whole giant monster of MHO("MHWO"?) would be really cool if it matched a much more difficult version of the Ubers in D3 and D2 only. I don't know how much fun it would be to have story bosses requiring the whole team making effect, or even rift bosses. Leave it for that secret/hidden/end game only type of thing.
All in all, the times are changing, can an isometric gameplay really work for 2020-2028 before someone else optimizes beyond Blizzard?