A small, primitive village has yet to discover fire, which is a good thing because there are highly flammable (but not otherwise dangerous) gasses in the air. The heroes, blissful in their ignorance, don't know that and think it a wonderful idea to show the locals open flame.
Unbeknownest to the character, he is in the royal bllodline. Suddenly the majority of royals fall ill and die, and the hero is left with the crown, but no experience or idea of what to do.
A Deity of some sort has unleashed a plague of bookworms or something like that in the area. Almost all spellbooks are destroyed, along with bardic and historical books.
Faerie foods with unusual effects. Like faerie sausages that turn the eaters into wiener dogs, faerie wines that make the drinker whiny, etc. There's a table in Palladium Fantasy RPG which has a table of ideas.