I am imagining a setting that involves a somewhat post apocalyptic setting. However, i don't want it post-apocalyptic in the way of the Dark Sun setting, or anything like Mad Max, Tank Girl or Waterworld. What i want is that the world was a standard, thriving fantasy world, and then something catastrophic happened that changed everything, but society has endured, recovered, and is back on the upswing. Post-apocalyptic, but without all of the baggage that comes with that term.
In that, i have decided that the Apocalypse was a war between the Faithful of the gods, and those that had turned away from their worship. The faithful lost, and as a final act of retribution, the gods called down a mass of catastrophes and horrors, deciding that if the world had turned from them, then it needed to be punished. However, once the dust had settled, the survivors picked themselves up, and began to rebuild society.
With that in mind, classes like the Cleric and Paladin, core classes and mainstays of Dungeons and Dragons as well as pathfinder would be far, far less common. In fact, most divine practitioners would be less common. They would probably still exist, but nowhere in the numbers they used to.
Instead, I am imagining a world where the Arcane and the Psionic are more common, with a leaning towards Psionics. Perhaps their was formerly a Deity of Magic, and for quite some time after the apocalypse, it was distrusted/unreliable, allowing psionics to become the dominant "Magic" type.
I haven't made much decisions on races, cultures, and other core classes, but at it's core, these changes are what is going to try to make the setting a little bit more unique.