It's that Sheldon guy. He's obviously a person with at least a touch of Aspergers. He's beyond brilliant, but completely lacking any social skills or empathy. He's constantly belittling and patronizing everyone he knows, from his roommate and friends to his neighbor and girlfriend. Yep, the guy even has a girlfriend now. He's incredibly insulting, but most of the time everyone around him indulges his oddity and even sometimes encourages it.
He has found people who understand him and are able to (comically) appreciate his quirks.
The understanding and compassion for Sheldon that his friends show is what makes the show, for me. In every episode he ridicules them endlessly (especially Howard, the only one who doesn't have a Ph.D), and they just roll their eyes and get on with their conversations. They get that this is just how Sheldon is.
Maybe it's because they are all smart, too. Maybe it's because they were all bullied and ridiculed and tormented when they were growing up. They know what social isolation is like.
At any rate, they all tolerate Sheldon's complete lack of pleasant personality and sometimes even seem to revel in his weirdness.
It was Bernadette, Howard's girlfriend/fiancé/wife, depending on which season you are watching, who said it best one day.
"Sheldon doesn't know when he's being mean, because the part of his brain that should know is getting a wedgie from the rest of his brain."
See, they KNOW. They get that he can't help being unempathetic. That it's genetic, and not a character flaw. They try to give him social cues, but in every episode, he's hopelessly disconnected. And it's fantastic.