No, I think the built-in setting thing is a thing. Even at the height of Fate's popularity, you weren't hearing about Fate Core as much as you were hearing about some of the licensed games based off of it, like Dresden Files or Leverage.
I think that going modular with "class"/career design, ala D20 Modern or even Star Wars Saga Edition, could potentially work well. Going the traditional 5e class-and-archetype route where multiclassing is an afterthought or charop thing would not be a very good fit.
They aren't part of the Big Two anymore, but World of Darkness hasn't gone anywhere; they just released a new Vampire: The Masquerade video game less than two months ago. For a long period Fate was basically the non-D&D/D20 system. Maybe the lack of a built-in setting hurt its staying power...
I once killed a PC with Diablo 3. Always a pity.
I'm enjoying Witcher 3 quite a bit but boy does Geralt control really clunkily. Navigating tight areas in particular does not feel good in the slightest