Invoked Apocalypse from Arcana Unearthed is a good choice. It covers an area of a 100 foot cylinder per level by 100 feet high per level, doing 10d6 of damage for one round per level. (It can only be cast once per year before destroying the caster.) As I understand it, it is now a 10th level spell in Arcana Evolved. (I never liked Apocalypse from the Sky as it seemed vastly more powerful than any other 9th level spell -- even with its rare material component.)
Staffan, check the Epic Level Handbook for ways to reduce the spell DC.
As for spells, the Invoked Devastation and the Rain of Colorless Fire from the World of Greyhawk setting were never detiailed, but each destroyed a powerful civilization. (The second spell, cast by the surviving empires of the Baklunish Empire turned the lands of the Suel Empire - which cast the Invoked Devastation -- into burnt dust. The Invoked Devastation is closer to the type of disaster which jeff37923 desires. No cities were left in the Baklunish Empire, only survivors.)
It might be best to just tell the story and not worry so much about the game mechanics.
Of course, natural disasters -- which humans or non-humans can trigger in a fantasy world -- can do a lot to reduce a population. Here are some sights for information on real world events. (I found some links while doing research on a new homebrew campaign that I am working on -- for various historic and prehistoric events.) Let's just say that either a rapid onset of an ice age or a supervolcano eruption would suffice to bring civilization in a fantasy world (and likely ours as well) to an end.
The Ice Ages:
Global land environments for the last 130,000 years is quite technical at times, but has tremendous maps. Read the bit on the Younger Dryas, which only took a few years to happen, for details.
The Toba Volcano: This volcano, now a lake in Sumatra, erupted violently some 76,000 years ago, triggering an ice age and greatly reducing the numbers of humanity then on the planet to perhaps a few thousand people. Here are some links:
Super Volcano Toba,
Toba Volcano,
BBC story on supervolcanoes,
Impact of Toba Explosion on human evolution,
Questions on "human bottleneck"
Enjoy the devastation.
