I’m surprised they haven’t done a My Little Pony Clue, considering Hasbro owns both. The story writes itself: A rogue changeling (perhaps Chrysalis?) has impersonated one of the Mane Six and caused some mind of trouble somewhere in Ponyville, Celestia’s Castle, Twilight’s Castle, etc. The goal is to figure out which pony is the imposter, where they caused the trouble, and what they used to cause the trouble (one of six magical artifacts, perhaps?).
 
If they want to throw a little damsel-in-distress into the plot (wouldn’t be the first time), the trouble in question could be Princess Celestia being kidnapped using some kind of magic artifact. In which case, the “where” indicates where she’s being kept prisoner (likely in one of Chrysalis’ cocoons).
 
There could be Friend and Foe cards that throw a little razzle-dazzle into the experience, like Spike, Discord, Shining Armor, Sombra, Tirek, etc. Discord could be in his own category as befitting the Lord of Chaos, performing such chaotic feats as swapping everyone’s positions around or reversing the turn order. Or he could show up as both Friend and Foe, reflecting his roles as both antagonist and protagonist over the course of the series. Princess Luna and Nightmare Moon could also be a mirrored Friend/Foe pair, with mirrored effects.

Fluttershy-Mr. Green  
Twilight Sparkle-Professor Plum  
Applejack-Colonel Mustard  
Rainbow Dash-Mrs. Peacock  
Pinkie Pie-Miss Scarlet  
Rarity-Mrs. White
 
I think these roles fit the characters well.

I’d buy that.
 
Also Flutters in a suit pleases me.