TwoSix
Everyone's literal second-favorite poster
I'm pretty sure the core 5e books are silent on the idea of what NPC demographics, and overall power levels within the setting, look like, so that's something any "5e based setting" would have to consider.What that would look like would really depend on what one decided the population of level 20 characters would be:, 1 in a million looks different than 1 in ten thousand.
Do you do something like Eberron where a level 20 character (or NPC equivalent) is a once-in-a-century demigod? Or something more like Forgotten Realms where NPCs who are level 20+ equivalent are rare but well-known?
Core 5e, to me, seems to have a tone of "abundance" and "cosmopolitanism", with lots of races and lots of monster species all having entire communities, rather than being one-offs or the subject of myth. And there are a lot of NPCs and monsters that are CR 10+, so I would probably lean towards a setting where at least Tier 3 level PCs and NPCs are known commodities.