I suddenly find myself thinking that I'd quite like to try out the upper levels of 5e play. Now, the reality is that I'll never get to play those organically, as I just don't have the time or patience for a multi-multi-year campaign to get there, so it would need to be something designed from the outset for higher level PCs.
I'm currently thinking of a concept where the PCs are each top-tier heroes in their own settings who are pulled together by a mysterious patron to explore some obscure corner of the multiverse. Actually, my initial concept has them as servants of no less a figure than Vecna, the god of evil secrets (and also of the Eye and Hand, and indeed "Stranger Things", fame). In which case, their interest would presumably be in some secret that even the gods are not meant to know.
Which works remarkably well - one of the more interesting bits of obscure 3e lore is that the Bastion of Unborn Souls is literally unknown even to the gods, so it's entirely reasonable to posit that there could be other such secrets. And, of course, if there is a secret redoubt of such antiquity that even gods don't know about it, who can tell what dangers it could hold?
And there's another thought... what if it was a Spelljammer adventure, thus killing two birds with one stone...