Regarding 5e, the problem is the saturation of unwanted setting assumptions in every aspect of the core rules.
Well, now THERE we agree. GURPs, the Hero System, and Chaosium pioneered the separation of "here are the mechanics" and "here is the setting" back in the 1980s. D&D *still* hasn't joined that revolution. PHB provides classes, races and spells suitable for play in the Forgotten Realms, and easily adjusted for Greyhawk. Not so easily adjusted for Middle Earth where "wizard" means something very different (and arguably not suited for PCs), and "cleric" should connect with Valar and/or Maiar rather than with Pelor or Lavanthar.