Depends on the disposition of the party. If they are your typical D&D style mostly-good-altrusitic party, then I usually just put them into situations that threaten the existence of the game world, and let them see if they can stop it. If they aren't the typical party (as IM current campaign, where most of the party is neutral or evil) then I mix it up a bit depending on each character's motivations. Currently, the party is motivated by some mix of revenge(the divine champion of Kossuth), powerlust (necromancer), greed (rogue) and fear (all of them).