In L. Sprague de Camp's 1942 novella The Undesired Princess the protagonist is transported to a world that follows Aristotlean logic, where everything is either one color or another with no mixing and shapes, besides the animals are all simple: The princess has hair that is primary color red; tree leaves are regular polgons of blue or yellow.
D&D as written often describes a world just as foreign as that. Even ignoring things that you could argue are merely abstractions for the sake of the game (like movement), you still have things like alignment (and in some editions alignment language), leveling, people with classes vs. nonclassed NPCs, clerical healing and the like.
I've read things in the past that posited a world where D&Disms got rationalized a bit (I've maybe written one), but discussion yesterday with a reference to the perennial "baby orc" argument made we think it would be interesting to throw rationalization somewhat out the window and play in a setting where the world just sort of runs on D&D (meta)physics.
We're talking about a world where some people start to develop superhuman resistance to injury and various abilities--and these keep increasing so long as they acquire treasure from underground hordes. Where there's some sort of metaphysical orientation to the universe that leads people to automatically acquire a language recognized by every member of the club when they join up. A world where sentients with lifetimes much longer that humans just can never learn to be better than humans in arms or magic. Stuff like that.
"But no!" You'll protest. "That would be really silly!"
Sure, but isn't that often the case with D&D?
See?
And this would actually elevate the silliness by making it a thought experiment.
All kidding aside, it perhaps wouldn't be the stuff of a long campaign, but I don't think the implications of that sort of thing would be interesting to think about.