There are many reasons why Lobo is called the Main Man. As the biggest, baddest bounty hunter in the DC Universe, he's worked for heroes and villains alike and can stand toe to toe with Superman. If he really wanted to, he could burn down the entire DC Universe and nothing could stop him - with the possible exception of a lizard.
If that sounds weird, the entire story told in Crush and Lobo #7 (by Mariko Tamaki and Amancay Nahuelpan) was even stranger. The Main Man's daughter proved to have her father's resourcefulness, as Crush got some space lizards to surround Lobo and use their strangely effective secret weapon on him.
Lobo's Strength is Undercut By Some Extremely Minor Flaws
In an unexpected turn of events, one of Crush's reptilian allies suddenly bit Lobo with its tranquilizing venom. Since the space lizard had space bacteria on its teeth, it managed to successfully get through Lobo's impenetrable skin, allowing the venom to take effect. This seemed like a pretty anti-climactic defeat for someone who managed to kill his entire race before he was seventeen.
In the miniseries Superman and Lobo, the Main Man's clones were defeated by exploiting another simple weakness. A genetic marker in their DNA made them susceptible to Czarnia's acid rain, which was able to bypass their regenerative abilities. However, this marker was built into the clones from the start, and they would have otherwise been virtually unstoppable.
Lobo is as Strong as Superman
Despite Lobo's pitfalls, his strength is certainly on the same level as Superman. DC First: Superman/Lobo #1 saw him go toe to toe with the Man of Steel for the first time and both were impressed to find that their strengths were on an equal footing. In one adventure, the Main Man went up against a Superman possessed by the demon Eclipso. Even though the Man of Steel didn't hold back like he usually would, the fearsome bounty hunter was still a match for him despite the beating he received at the hands of the Kryptonian.
Lobo's strength is equal to Superman's, but he doesn't have his own kryptonite outside of lizard-born space bacteria. However, the Main Man is still effectively immortal because neither Heaven nor Hell wants to take responsibility for him. On prior visits, Lobo beat up all the gods in Heaven and actually enjoyed the torture of Hell. Despite all of this, he still suffers from an incredibly simple weakness. While it does somewhat damage his fearsome reputation as the Main Man, it is no doubt a good thing that there is something in the universe capable of taking him down easily.