As Remathilis says, there's a difference between "Not unless the DM says okay", with an ultra-cosmpolitan setting where there very well might be enclaves of Gnomes or Dragonborn or the like, and a setting which actively and aggressively sets out the limits of what is in it, as an entirely intentional conscious way of differentiating itself from and distancing itself from other D&D settings (not in a hateful way - just to make it clear it has a very different approach and set of interests).I can see certain classes and subclasses being a problem, along with the limited spell selection, but as for the issue of certain core races not being playable and the lack of explicit divinities, isn't that the same situation as Ravnica? And I believe that turned out okay? Nobody was really raging about not being able to play a gnome or dragonborn in that setting.
Defiling and Preserving by themselves present a serious challenge, mechanically. Defiling has to be the default, or the setting concept breaks down. Mearls suggested one approach, but it was a very bad one, because it makes Preserving the default, and Defiling an unreliable way to gain a short-term advantage (at the long-term cost of marking you for death). It also ignored the fact that even Preservers defile, they just do so in a controlled way. If Defiling and Preserving works the Mearls way, Dark Sun wouldn't be in the state it is, and 99% of arcane spellcasting would be done Preserver-style, because only if you're in a terrifying life-or-death situation does Defiling make sense. Instead you need to have a situation where to be a "full-power" arcane caster, you must Defile. Is that "fair"? No, but that's the point - Dark Sun isn't one of these "everything is fair" settings. A number of 3PP 5E settings have situations where powerful arcane magic gets you in hot water I note so it's not even that exceptional this edition. Also you'd basically have to invent a clear distinction between arcane and non-arcane magic which 5E doesn't make (but 2E did).
For a lot of players, and this happened back in 1992, as well, this is initially quite angering - this idea that arcane magic is inherently bad. And I think WotC would be very, very sorely tempted to simply er, "Defile" Dark Sun rather than upset them, even though they'd get over it in a few months/a year.