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.
A certain type of demon cannot not be hit by ranged weapons or attacks. Attacks have to be made up close and personal for the damage to mean something. Ranged attacks are to impersonal.
Possibally a way to make the ranged attacks more meaningful would be to coat the arrow head or what not with the shooters blood. Of course, they'd better be a good shot, otherwise they're wasting arrows and already bleeding to boot.
Spells: wizards might have half or no effect, preist might work due to divine intention.