A new 5E setting should be...
...the 4E setting.
No, wait. Hear me out.
I'm not talking about the Nentir Vale, which (to me) has somewhat old school vibes. (The creator, Richard Baker, also authored Lost Mine of Phandelver, Red Hand of Doom, Reavers of Harkenwold. They've all got a similar feel that I would argue is NOT the fantasy superhero vibe of 4E.)
Instead, I'm talking about the broader 4E multiverse, as well as Nerath, of which Nentir Vale was just a small part.
Check out the map below. It's a greatest hits of D&D adventures, locations, themes, and monsters. Evocative...if not original. That "greatest hits" approach is one of the defining characteristics of 5E.
5E also has a maximalist approach to playable races, which would need to be a key part of any new world. Well, 4E had the same approach.
There's a lot of 4E lore that carried over to 5E. The Shadowfell, the Feywild, even the "First World" bears a lot of similarity to the implied cosmology of the Dawn War.
Finally, while 5E doesn't present as being a fantasy superheroes game like 4E...it kind of is. Especially in how it plays at the table. And that's even more true with 5.5E.