Mack Salmon is a villain who first appeared in Night of the Gilded Heron-Shark.
Appearing as a human with a fishbowl for a head, Mack Salmon is really a fish who travels on top of a fake body. He blames Sam and Max for causing his current form through some incredibly vague past incident (which they have no memory of) and is perpetually seeking revenge against them. He likes to revel in self-importance and see himself as their arch-nemesis, but in reality he is little more than just one of a variety of bizarre enemies they've come across.
In Night of the Gilded Heron-Shark he and two goons confront Sam & Max simply by waiting for them in the office, but are thwarted by the timely appearance of The Rubber Pants Commandos. In the animated series he returns as a more typical evil mastermind using some more elaborate plans and is arguably the most competent enemy they face.