The Sicily campaign was a disaster, and a massive waste of resources. Perhaps it would have been wiser for Athens to concentrate it's fleet closer to the Greek mainland. I was thinking that the plague of Athens in 430BC was a major contributing factor to it's defeat in the long term. The plague cost Athens one quarter of it's population, and therefore manpower.
If the plague had not occurred, or even better struck Sparta, Athens would have been significantly stronger. I know it seems all too easy to attribute Athens' defeat to such a simple event, but most of history's major turning points have been determined by such things.
However, any creative and original POD's would be welcomed. I must admit that I didn't put a lot of effort into mine. Bonus points for plausable descriptions of how the Classical known world might look under an Athenian hegemony.