* Three Robot Masters [[OneHitKill die in one hit]] (or two on Difficult),
** Metal Man. You fight him again in Wily Stage 5 and if you use the Metal Blade (his own weapon) against him, [[WeaksauceWeakness he dies instantly]]. He's the only Robot Master in the series to have [[HoistByHisOwnPetard such a crippling weakness to his own weapon]].
** Wood Man to Atomic Fire at full charge.
** A well-placed aim by the Air Shooter's tornadoes can kill Crash Man in one shot.
* Bubble Man is supposedly the ButtMonkey of the Robot Masters. His weapons are pathetic, he has several [[WeaksauceWeakness Weaksauce weaknessess]], and a crippling design flaw makes him unable to walk.
* The weakness of the Picopico-kun boss in Wily Stage 2 is the next-to-useless Bubble Lead.
* And again with the [[spoiler:Fake]] Wily Alien. It absorbs every attack you have except for, of all weapons, the Bubble Lead.
* Even after you defeat the final boss, Wily still continues to control the hologram, until it makes a comical whistling noise indicating it's about to give up the ghost and then stops working.