The cure of cancer that makes life better
The time of every heroes weakness/death is the pivotal turning point in either myths or movies, but that also means it was the end of an era for many heroes. There are many counts of Superman’s weaknesses exposing him in both comics and films. Although it was never told in any storyline that kryptonite has actually killed Superman, but it has nearly killed him but weaken him into a very sicken state. It is mentioned that as long as Superman is exposed to it long enough, any villain would be able to kill him.
In an imaginary tale, the long time arch nemesis Lex Luthor comes up with a way to kill Superman; the original death of the hero appeared in the Superman #149 comic that was issued in 1939. Their rivalry began back in the 40s, but Lex knew that he could’t resort to brute force to kill Superman so he used his intellect and science using some form Kryptonite to kill him. This was also when Superman was exposed to his major weakness.
Lex Luthor was released from jail following his invention of a cure of cancer that makes life better for all. That was when he tricks the Man of Steel into his lab, and was trapped by him while Lex Luthor bombards Superman with green kryptonite rays and later injected a lethal dose of Kryptonite to finish him up. In other comic issues and also in films, there are other villains that eventually weakens and/or kills Superman with his other known weakness. But this rival with Lex Luthor was the most well known throughout the era.