In the comic, Title Characters are the brothers Bob and George who have their names in the comic strip's title and therefore The Author doesn't let them be killed. This fourth wall breaking immunity was first mentioned in January 8, 2001, right after Mega Man claimed he couldn't be killed because he was a main character in the comic. Bob than pointed out that his name was in the comic title, and that the immunity applied to him. After "destroying" Mega Man, Bob told George that he didn't get these title character benefits, but this has been proven to be untrue.
This immunity has then been referenced several times, when a convoluted plot device saved Bob or George's life in a seemingly hopeless situation. In the comic of March 18, 2004 however, George was actually killed in battle. The Author then later brought him back to life, showing that title characters can be killed, just not permanently unless The Author is first taken care of.
After Bob's apparent demise in a climatic battle, the comic's title was temporary changed to simply "George: The Comic Strip", giving the idea that Bob could and did permanently die. However, this was later proved false when he was revealed to be stuck in an alternate dimension.
As George temporary died at one time, it appears that title characters aren't really very much different from the rest of the main cast, of which none have permamently died.