The Venture Bros. ended its first season on a traditional episode. But, it turns out this [adult swim] show doesn't make use of Negative Continuity, and in the first episode of season two, we find out that the titular brothers are still dead and that the Monarch's still in jail.
Then there's Brock suddenly up and quitting as he couldn't take the weirdness anymore at the end of Season 3. That episode also included the death of 24 and the obliteration of all of Hank and Dean's spare clones.
The season four premiere makes it even Wamier—Sgt. Hatred is the new Venture bodyguard, HELPeR is now THE WALKING EYE!, Hunter was The Mole in the Blackhearts organization and brings Brock into SPHINX, which is now operating on the side of good, and the Brothers' looks have changed for the first time ever—Hank grows his hair out and starts donning Brock's old jacket, while Dean now has a wispy little mustache.
The season 04 finale "Operation P.R.O.M": General Treister retires and leaves Colonel Gathers in charge of OSI. Molotov Cocktease was the rookie SPHINX agent seen in the background of previous episodes. She steals Monstroso back from them, claiming that he is her lover. When Brock corners her in a stolen limo on the edge of a cliff, he threatens to let Monstroso fall to his death. Molotov knocks Brock off of the hood of the limo willingly and the car falls and explodes with them both inside.