the artifact
There is always some sort of artifact or talisman: the sword, the ring, the magical knapsack of power and truth, etc. Mysteriously, the villain's weakness just happens to correspond to some artifact that is known by the guide (this is the one thing that makes the guide not so useless), often a repeating history motif is employed to explain this. eg. the sword was made to defeat the villain the first time, but he has come back, and for some reason it would be too much work to try and make such a weapon again, the smith died or something, , so we have to have to go find the original.
Either the artifact must be found, or the heroes possess it and must do something interesting with it: use it to kill the villain, destroy it, reforge it, put tab A in slot B etc.
If the artifact is the object of searching, it is never located in a museum, nor some rich nobleman's collection of weapons, or any place that one would normally find ancient stuff. Instead, it is guarded by fearsome beasts, treacherous traps, magic spells, and riddles. Never does it require the hero to pick up a shovel and dig through ruins, grid off a dig site and systematically search for the thing.
If our artifact is in the "do something with" category, the doing something requires finding a person or location or another artifact; the character never lives close to someplace where the doing something can be accomplished.(see note on plot above).
(Joe Campbell would love this thread)