Dark Sun though was the ultimate example of a setting breaking the core rules to fit its tropes. The 2e era setting often resembled D&D In Name Only, with everything from races to classes to ability scores and xp tables changed. That kind of radical alteration to the core game wouldn't work under WotC's current design paradigm. There is no way WotC would sell a setting that that used 33%-50% of the core rules as is and nearly none of the supplemental material. They want a setting that would sell PHBs, not piece-meal replace them.
That ultimately puts the setting into a kind of limbo between wanting to be a D&D setting and wanting to be this radical departure from it. If it wants to be a D&D setting, it needs to accept more of the D&D tropes and options like the 4e version of the setting did (that includes finding homes for every class and most races). If it wants to emulate the 2e version and have radically different classes and races than the PHB, then it needs its own PHB (and that would come in the form of a spin-off game).
That really holds true for any setting, IMHO. Settings should flavor the core D&D setting, not replace or radically alter it. Forgotten Realms is vanilla D&D, while Dragonlance should be heroic/romantic fantasy, Greyhawk pulp, Eberron pulp/noir/magitech, Ravenloft gothic horror, Birthright political intrigue/dominion, and Dark Sun post-apocalyptic pulp. The PHB should be valid (with some minor changes required for flavor) in all of them. A new player should be able to use just his PHB and make a viable character with some small adjustments (such as in the areas of subraces, equipment or backgrounds). Options should be adapted when possible (half-orcs = calibans, dragonborn = dray) or if an option isn't available, its replaced with another equal option (no gnomes, but here are muls on Athas; all halflings must take the kender subrace on Krynn). Additional options (psionics, artificers, new races, etc) should be balanced enough that if a DM wants to use them in another setting (be it his homebrewed version of the Realms with warforged and psionics or a complete new setting) they are usable without imbalance to the game. Settings that cannot abide those rules should either be ditched or farmed out to 3pp as stand-alone games.
Ultimately, I actually think the July product we'll see might be a UA-style primer that tests fan reaction to updating those settings to 5e. How will fans react to Athasian paladins, Krynnish warlocks, Oerthian dragonborn, etc. Feedback gathered will go in the product coming next year. It might be the best way to take the fans temperature for how much they can make settings conform to the Core Rules and how much they can make the Core Rules conform to the settings...