4. Kryptonite (Superman)
Probably the most famous and obvious weakness suffered by any character in fiction is the weakness to Kryptonite suffered by Superman. Indeed, the Kryptonian element has become synonymous with weaknesses in general, with people (both fictional and otherwise) referring to anything that weakens, hampers or scares them as "my Kryptonite" on a regular basis. Superman is extremely powerful, possessing super-human physical strength, speed and durability as well as a whole host of more exotic powers such as flight, heat vision, X-Ray vision, freeze breath and super-breath, but these powers are all diluted or negated when he is exposed to this material from his home planet. The extent of the effects differs depending on the writer's mood. Take Superman Returns for instance - one minute, being on a large landmass of Kryptonite renders him vulnerable to a kicking by human flunkies, the next minute he's lifting the entire thing in to space (which causes him to collapse, but still...).