Main cast meets killing joke.

[Kashin]

I came up with a few truly horrid one before sleep last night.
Luna: "I could tell by the screams of the children as they run away" Luna becomes a phantasmal horror (D&D monster, hasbro has rights to it) where she appears as the physical embodiment of the deepest fear of any pony who sees her. Almost every pony would run from her in terror regardless of her actions and some may even keel over from heart attacks.

Scootaloo: "I'll never come up with anything. Never. Never. Never" She loses the ability to learn. She will make mistakes and know she will always be doomed to repeat them and never improve.

Snips: "well mine is heaver" He becomes the heaviest pony in history, slowly dieing under his own weight like a beached whale.

Snails: "well mine is bigger" His head or other body part grows to such titanic size that he can no longer move and slowly dies of exposure.

Applebloom: "I'm doomed, doomed. I'll never find somethin I'm good at." She loses her cutie mark, special talent and will live the rest of her life knowing that she isn't special and never will be.

[ChaosMedler]

hmmm, if this is based of Fallout E before the bombs then there would have to be also long term as fluttertree *shudder* is around for over 200 years...
I try to think of this as an exploration of their charecter with some fear or 'worst nightmare', makes makes this feel easier.

Applebloom: Everything she will try to build/create will kill and kill
Scoot: She finds out all her stable 'plans' make 'everything' the bombs and fallout happen again... harsh
Spike: all his surveillance equipment is destroyed, thus becoming completely secluded from the outside world... and he can't leave... nothing but him and the cave... how do you think spike would be without the spritebots?
Luna: by her power, the moon falls... on equestria
Celestia(now SPOILER.... she is in maesebs): She sees, hears and 'feels' all the pains and sorrows in equestria what if all her senses were turned up.
Sweetie Bell: she gets her cutiemark and it's the picture of a broken music note...
D. Hooves: everyone has the urge to hate her... i really couldn't bear to do that...
Dash:... I couldn't
Twilight: magic overloads randomly, as bad as the time she needed Celestia's help, when it overloads, people and friends around her turn into 'common' and 'unimportant' objects... based off her life changing moment with friendship, to steal 'that' is like stealing the show...
Applejack:........ *sigh* an emotionless merchant of death
???Steelhooves???(just a thought): becomes filled with blind rage

[Mister_Clacky]

Hmm... for Dash I would go with...

this

Her hooves and wings turn to iron, robbing her of her speed and her ability to fly. Not quite as cruel as that Pinkie idea though.