The most well-known example is Superman and kryptonite. It is so embedded in pop culture knowledge that kryptonite has become synonymous for someone's weakness. And honestly, kryptonite makes some sort of sense, it's radioactive pieces of his home-world which weaken Superman and strips of his powers. Which makes sense since it's radioactive to him. Radioactive stuff is bad. We all get that.
|Kryptonite bites are bad too.|
Of course, writers had to get 'creative' and introduce other types of kryptonite aside from the common green variety, like red kryptonite which turns Superman into a dick who likes blowing out the Olympic Torch or straightening the Leaning Tower of Pisa.
|"Straightening ancient architecture. I am so evil."|
Similarly, Batman also has a weakness. It's called Bruce Wayne. Whenever, Batman is out of his batsuit and just chilling as a playboy billionaire, you know that he's going to get the crap beat out him.
|Just to clarify, that's Bruce under the rubble, out. His geriatric butler has to save him... because he was out of his batsuit.|
Although, possibly the most you-must-be-joking-there's-no-way-that's-their-weakness is that of Power Girl's. Power Girl, in addition to having breasts no mere fabric can contain,
|What you're missing? Look in a mirror, I think the answer will become apparent.|
Also has a very specific weakness and that weakness is essentially anything. Anything natural and unprocessed, that is. Like a tree branch.
|Yes. A branch. Not a special magic branch. Just a normal branch from a normal tree.|
I don't want to elaborate on this further as it was covered in Cracked.com's brilliant The 6 Most Ridiculous Superhero Weaknesses, but it leads nicely to the weakness of one of the most powerful superheroes of all time who they did not mention in their article, Green Lantern.
|Oh yeah. This guy.|
The original Green Lantern, Alan Scott construct his ring and lantern following instructions from a mystical green flame, and his ring work more on the basis of magic than the pseudo-scientific rational of the Green Lanterns to follow, who were part of the Green Lantern Corps, the intergalactic police. But Alan Scott's ring had a weakness. Wood.
|Well, maybe if he didn't have a weakness to wood, he wouldn't have.|
Just to be clear, Scott can use his ring to create a shield that could protect him from bullets, fire, missiles, laser beams, and/or super-punches. But throw a stick at him and it passes right through his shield. Not only that but it makes him older. Since his ring keeps his body in a form of stasis, he doesn't age. However, his in addition to the fact his ring has no effect on wood, wood actually stops his ring from working, thus aging him.
|Doesn't that happen to everyone?|
When DC decided to revamp the character for what became the Silver Age of comics in the 1950s, they removed the magical elements of the original and replaced them with science fiction tropes. Thus, the new Green Lantern's (Hal Jordan) ring was technically, not magically, powered by the Guardians of the Universe's master power generator which his Lantern accessed. Oh, and they remove the weakness to wood because they realised that it was silly. Instead, his ring was useless against the colour yellow.
|Of course, it doesn't. That doesn't change the fact you got taken out by a lamp. A lamp.|
This weakness to the colour yellow is due to an impurity in the Guardian's master power generator. This is later found to be because yellow is the colour of fear as green is courage in the DC universe, and to overcome the weakness to yellow the Green Lantern has to accept and conquer his fears. However, this does not erase over 40 years of comics when stuff like this happen:
|Dammit, it's yellow. My ring won't work on things that are yellow. I'll still zap green beams to look useful.|
Actually, there were a number of Green Lantern comics that revolved around the weapon/villain which was, for no discernible or logical reason, yellow.
|Why is the pterodactyl yellow? No, seriously, I want to know. Why?|
And obviously, this weakness is one villains could easily exploit if they ever found out about it.
|Yeah, Mister Mxyzptlk owned Green Lantern with a giant banana one time. And yes, that is Bat-Mite in the background. And I think Wonder Woman just had a DUI.|
So, obviously the two generations of Green Lanterns' most fierce enemy would be an evil sentient yellow lemon tree.
They probably hate this song. Lemon trees everywhere.