@Rubber Johnny  
There are different ways you can go with it. Maybe ponies are genetically modified lifeforms humans made to be servants and companions, maybe humans died from exposure to magical radiation but some turned into ponies, maybe there was a virus that killed or mutated most of the population but somehow created ponies.
 
For the first I always had an idea of humans attempting to terraform an alien world, creating an artificial sun because the planet’s own sun is too far away, and creating lifeforms that were meant to manipulate the environment and make it imitate earth, and throwing in some artificial creatures inspire by mythology to entice colonists to make the journey. Ponies were meant to control the weather, grow the food, care for the ecosystem, and the unicorns were meant to be servants to the humans as well as make the two moons imitate the earth’s sun and moon.
 
Something went wrong and the colonists never showed up. The few scientists never received contact and had no way to return to earth, so they grew old and died. Eventually all the creatures forgot about them.

@Background Pony #57F4  
It is sort of an interesting idea, that pony civilization is really built off of a post-apocalyptic human civilization.
 
I guess it would be something like the movie 9 – humans get killed off but another, animated lifeform with the same essence as humans lives on.
 
Maybe I’ll turn this into a fic eventually…

Pictures like these make me think of a kind of post-apocalyptic setting where there are very few humans left but somehow ponies have moved in too, and most of them live in tiny scattered villages made up in the remains of human cities and towns.