It’s a generally-understood character development device in comic-dom that, when you have an immensely powerful superhero, he or she should have one unconventional weakness. This probably serves more as an aid to writers and future plots – to more easily imperil the hero for dynamic story lines.
A Singular Weakness for an Otherwise Unstoppable Force
Kal-El of Krypton has perhaps the most famous weakness of them all – the radioactive piece of his dead home world, Kryptonite. When the planet Krypton exploded (as predicted by Superman’s scientist father), shards of the deadly core followed the infant’s rocket-ship on its path the planet Earth.
Although Kryptonite wouldn’t become a significant element for many decades, it is the single thing that seems able to harm Superman immediately, greatly weakening him if they’re in the same vicinity and the element isn’t shielded by a lead container. Clark’s powers begin to wane very rapidly, and even a normal human can harm him. Once it is moved several meters away from him, his massive powers are restored.
Depending on the writer and particular incarnation of Superman, Kryptonite isn’t very safe for humans either; the extent of the damage is similar to other radioactive elements, however. It hurts humans over time – as opposed to all at once. The villain Metallo and a super-suit belonging to genius Lex Luthor are both powered by Kryptonite, which is the only thing that allows them to stand toe-to-toe with Supes in certain battles. In others, Clark fights from a distance, defeating them with his heat vision or by throwing heavy objects at super-speed.
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Another weakness of Superman’s is far more difficult to come by, as the eligible opponents are few and far between: beings of monstrous super-strength. Although this weakness is hardly exclusive to Clark – after all, anything strong enough to physically hurt him would outright kill most other heroes – it bears mentioning because of the exclusive class of beings whose strength actual imperils Kal’s life. Obviously Doomsday takes the top spot, then Darkseid (and just barely at that; despite being a god, Darkseid has always seemed capable of putting a beating on Clark, but not quite being able to kill him even in principle).
After these two, the list extends to any possible Kryptonians still mulling about in corners of the galaxy – such as General Zod. In fact, from the look of the new trailers for the Superman movie, the lost Kryptonian General Zod and his crew of two others looks to be the primary challenge the Man of Steel faces.
Extent of Clark's Powers
Since Clark is powered by the Sun, it is possible to gain an advantage on him by somehow shutting him off from yellow sunlight. Although this is a weakness, it is very, very difficult to come by because you need an immensely powerful being that can fight him for half-a-day and cause him to drain his stores of energy.
Since Superman could probably boil away an ocean with his heat vision, or move mountains all night with no reduction in stamina before sunrise, this isn’t a feasible weakness without finding an equally-powerful threat. Alternatively, you might use magic to transport him to a planet with a red sun, because red sunlight strips him of his superpowers.
Lastly, Superman Man of Steel is moderately susceptible to magic. Since no one can really move the Man of Steel with physical force, the facts that the magically-inclined can summon spells or use mystical artifacts to have some effect on him that registers should be considered a weakness. Nonetheless, it’s important to understand that magic doesn’t render him at all helpless; as in, you can’t expect to kill Clark with a spell or anything – just make life more difficult for him.