The setting is also something I need to consider. We're playing a classic fantasy setting (not steampunk or sci-fi) so I could set it in Dragon World or Lodestone, but I could also create something unique. Personally, I was a fan of the short-lived cartoon The Pirates of Dark Water and wouldn't mind running an adventure in that Waterworld-esque setting. I was also thinking of a Machu Picchu-style campaign city with the "dungeons" being mountaintop ruins.
It can't be too involved as we might not even have two full days of playing, and this could be the only time that we ever play with these characters. I could have a couple of options ready and go with the one that their characters seem to fit best. One way or another, my mind is buzzing with possibilities.