As any character, grab the machine gun at the lower left of the screen. Use any weapon to hurt the Boss. When he goes to recharge, run to the big window in the room and unload your Uzi, Shotgun, Chainsaw, or other weapon into it until it breaks open and the Boss dies. You can pretty much ignore him when he returns from getting charged, since you will be standing on a Health Glyph while destroying the window. Vampire and sunlight equals death.

When you get to the last Boss, do not free the three locked up innocents unless you have low remaining lives. Freeing them will make the Boss have two more images of himself, creating three Bosses, but only one will be real.

When playing in multi-player mode, have player one destroy the window while the rest of the players harm the Boss.