Well, Agents of SHIELD, sort of, since the lead of the SHIELD comics it's credited as being based on was Nick Fury.
Batman Beyond comes close, since Terry McGinnis was a "Batman" with no precedent in the comics; though Bruce Wayne was still a lead character, so it's borderline. And you could quibble whether The Incredible Hulk's "Dr. David Banner, physician, scientist" is the same character as Dr. Robert Bruce Banner, nuclear physicist.
Outside of superhero comics, there's iZombie, whose lead on TV was Liv Moore instead of Gwen Dylan. The Timecop series replaced the comics' Max Walker with Jack Logan.