Favorite Times a Game Punishes You For Using Cheats
What are your favorite times a game punishes you for using a cheat? Bonus points if it's a cheat that's actually in the game proper and not like a GameShark.
In Banjo-Kazooie, if you use too many cheats that open the Note doors in Gruntilda's Lair (that you need to collect Notes in the levels to open normally) Gruntilda will get super mad and threaten to wipe your save. If you use one more after that point she comes back and says "I warned you, bro!" And actually wipes your save file and starts you over at Spiral Mountain.
Honorable Mention: if you use a Game Genie in Super Mario Bros 3 and beat Bowser, the game pops up a green permanent PAUSE that you can't clear right as soon as you go through the door to Peach and won't let you see the ending.