I have not been able to play 5e until now, so I'm not sure about it... But, knowing that 5e is all about a robust, lightweight core and optional modules, it would make sense to imagine modules that would morph D&D 5 into something else.
For example, what about an "Ars Magica" module or a "L5R" module ?
Back in the 3e days, some games received the "dungeonification" treatment, like L5R (causing, of course, fan uproars and internet wars...). I wonder if WotC had this in mind. And I wonder if it would be easier with the new system and its flexibility to recreate the "feel" of other games.
I think the DMG will help us see what is possible there.
The 5e presented to us so far is simply D&D -- dungeons, monsters, wizards, warriors, entirely it's own genre D&D.
But the underlying mechanics may not be so "D&D."
Lets take, say,
Call of Cthulu as a baseline. 3e did a CoC d20, but it didn't show the flexibility of 3e as much as it showed the limitations of the game. Levels? Hit Points? Crits? A CR for Cthulu? Clearly these mechanics were suited to heroic fantasy, but they don't apply to semi-modern investigative horror. Many of 5e's mechanics (including levels, hit points, crits, Challenge, but also things like bounded accuracy) are similarly unsuitable.
But then you can probably make a 5e hack without those things, and introduce new concepts and mechanics to cover elements of investigative horror, and keep the same basic pacing in place. Like, if I were to take 4e (D&D's most flexible so far) and crudely apply it to that genre, I'd probably treat mysteries as monsters and HP as sanity and attack rolls as looking for clues and healing surges as visits to your psychiatrist, etc. So on a strong enough math chassis, there's certainly the possibility for creative flexibility that leads to different experiences. Instead of goblins killing you with swords, you have a mystery that is driving you slowly insane, but a lot of the numbers and rolls remain the same.
So the hinge here is in how flexible the underlying maths of 5e are, combined with how much an individual designer would be creative in re-interpreting them for a new genre. A designer that just thoughtlessly leaves in a mechanic like levels or hit points, or a game that can't abide a manipulation of those things, is not going to be flexible enough to deliver a satisfying experience in multiple different genrea.
Which is probably still fine, if that's the case, though I'd be sad at that loss of flexibility from 4e.