The Boss is based on Gus' boss, who fired him for working on his video game. His weakness is red ink. Red ink (in the red) signifies losing money. There was nothing his boss hated worse than losing money.
The trivia item below may give away important plot points.
The second villain, "Evil Shirley" who is based on Lauren's (Cynthia Gibb's) mother, fires icicles at her foes, and her weakness is mud, because Lauren's real-life mother is such a compulsive neat freak. The only way to kill her, is to drop a house on her (she's later hit by a motor home).