Even Superman has his vulnerabilities, but two of his most well-known weaknesses could potentially be a lethal combination. An orchestrated attack paired two of the Man of Steel's Achilles' heels together and made a powerful anti-Superman offense.
Every superhero has a weakness of some sort, and a hero as powerful as Superman has more than a few. The most popular, by far, is kryptonite—radioactive slivers of his home planet after Kryton's devastating explosion. Not only do the space rocks have a powerful effect on Superman and his fellow Kryptonians, the material comes in a number of varieties and colors, making kryptonite exposure highly dangerous and unpredictable. But kryptonite is just one of Superman's weakness. The hero is also vulnerable to red solar radiation, which robs him of his powers, as well as magic which can completely disarm the hero.
But what's the right combination of weaknesses to really hit Superman where it hurts? The answer was revealed in Action Comics #880 by Greg Rucka, James Robinson, and Julian Lopez. Superman allies Chris Kent and Thara Ak-Var, aka the current Nightwing and Flamebird, are keeping an eye out for Nadira and Az-Rel, two sleeper agents working for the evil villain General Zod. As fate would have it, the two Kryptonian rogues interrupt Nightwing and Flamebird's search and force the heroes to pursue them. Thara and Chris give chase, following their enemies into an abandoned subway, only to be critically injured by blasts of kryptonite. Before Flamebird or Nightwing can figure out what's going on, the heroes are beaten into unconsciousness. It turns out that Nadira and Az-Rel were actually the kryptonite-powered villains Metallo and Reactron in a disguise, courtesy of magical villain Mirabai.
Granted, arcane forces are often used in a more direct capacity, as it allows magic-users to circumvent Superman’s many powers. But Mirabai and her compatriots figured out that they work just as well in a support capacity. After all, kryptonite is probably the Kryptonian people's most effective weakness, and exposure is enough to seriously harm them. But as shown here, magic can give villains that extra edge to really hurt someone like Superman when they pair it with kryptonite.
When it comes to pure lethality, nothing matches the deadliness of kryptonite. Depending on the variety, it can either kill, mutate or completely depower someone like Superman. However, it can be hard to get the jump on someone who can use X-ray vision and see kryptonite coming from hundreds of miles away. But magic could easily help a rogue slip kryptonite under the Man of Steel's radar. Like how Mirabai easily disguised Reactron and Metallo, any other evil user of magic could hide the radioactivity of kryptonite. Any villain could make sure it's in Clark Kent's proximity and simply wait until it's too late for him to do anything. So, while Superman might have a workaround for kryptonite or magic, but together, they might be the most dangerous threat he's ever faced.