“ A village where everyone goes blind sometime during puberty. What could be causing this? Perhaps something in their diet. Or some malignant gene. How would an entire village where only young childen can see function?”
“ A dark necromancer has discovered a way of making the magical energy cost of resurrection less than the energy he can gain by draining their life force. Given a sufficient supply of mind-drained minions, ultimate power beckons.”
“ The PCs are accosted in a major city containing at least one famous fortuneteller / prophet of the future. They are informed that their as-yet-unborn child will (insert terrible evil), and that, although they are very sorry, the PC must be executed to keep this from happening.”