The boss in the Chemical Plant Raid in Lethal Enforcers. How the fuck are you supposed to kill a guy in an Apache Assasult Helicopter with a Revolver?! Nevermind the fact that even if you manage to survive with a shotgun or grenade launcher thru the stage, it was hell trying to figure out how to shoot the guy. It ended up like taking 5000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 rounds just to beat the guy.
And, I forgot the name of the game, but it was a Western-type shootout where you stodd in front of a mount with a gun in it, and you had to "draw" like in the Westerns. The last Boss was (I believe) a master sharpshooter, and his reaction time was less than 1/2 of a second. The bad thing about the game thought was, if you "jerked" the gun even a smidgen before the time to draw, the computer would "scold" you for drawing too quickly. Not to mention the design of the holster was bad to begin with.