Not so much gone, as the ancient empire were all posthumans and the other races were their spawn. Now, the few remaining humans are pretty much seen as throwbacks by the other races—as you say, races created by the posthuman empire who now rule the world.

(more random setting wibbling in the reply to razorsmile below).

Also see reply to mythicfox, below.

Kinda. Take Clarke's Third Law and apply it to D&D.

The basic setting conceit of 4E is "points of light", a small bunch of walled settlements in amongst an unknown wilderness; a great empire used powerful magic to unite the world and know the unknowable; dungeons are their strongholds, long since lost. So the ancient empire was a posthuman civilization, but nobody remembers more than dangerous stories about the Precursors. Heroes have a fragment of their posthuman ancestors by whatever means (memes that can breach the Planck barrier between ideas and matter?) and delve into dungeons in order to reclaim their heritage.

I've got random ideas about six space elevators leading to asteroids—the Spire-Cities with their tethered moons. Thing is, only two remain connected. One's gone completely, the remaining three are in orbit.

...yeah, I'm jonesing to run D&D but can't be fucked with boring default fantasy settings.

General theory: Heroic Tier is all about discovering the secret history by uncovering lore in Precursor ruins, and ends with re-activating a Sentry-City (each Spire-City has eight Sentry-Cities dotted around, maybe a 500 miles distant. Spire-Cities are about the physical size of New York City, Sentry-Cities are satellite colonies each the size of Tokyo. All the urban metropolises are now carved up into a handful of actual cities and a shitload of urban wilderness) as their home-base. As such, they also stick two fingers up at the Auspices of the Spire-Cities, and have to deal with the fallout.

Paragon is the PCs inheriting their birthright, dungeon-diving to activate lost systems and fast-tracking the world to a post-industrial society that's still based on magic (Clarke's Third Law) and with a mindset that's thoroughly Mediaeval Fantasy. So Factory-Cathedrals churn out golems to take on manual labour, and the PCs might activate a Circle of Creation that can summon any mundane object the owner desires (not magical objects, of course). End with them travelling to one of the Tethered Moons and activating the Sentry program (one fuck of a boss fight, natch).

Epic involves handling the fallout from the other two tiers. Sure, they're badasses but they've got to handle the sociopolitical ramifications of their actions. They're pretty much the only heroes who haven't been co-opted by the Auspices, so they're going to face similarly uplifted heroes who just want tomorrow to look a lot like today.

I've half a mind to write this up properly. All these parenthesis-as-I-think-shit-up gets annoying after a while. Also, terminology subject to change.

If you do, let me know how it goes!