Please, these ponies don’t know my Dokapon Kingdom. The definitive friendship destroyer game!

JUMANJI!

@Liberion: I love Dominion, but since graduating from college I can’t get anyone to play it with me. Ah well. I guess that’s what makes Isotropic great.
 
Agricola and Twilight Struggle I haven’t tried yet. And it took me a moment to see what you did there.

Twilight would be playing adult board games, like Dominion, Agricola, or…Twilight Struggle, yeah!

Monopoly? Boring!
 
Gimme Scrabble anytime!

I bet Twilight would insist on following the auction rules for declined purchases and calculate the interest on mortgaged properties, Dash would steal 500s from the bank when everyone’s back was turned, Rarity would only buy properties from the reds and above (no filthy Old Kent Road for her), Fluttershy would accept every trade other players proposed no matter how unfair, Applejack would cling fiercely to the utilities despite their uselessness, and Pinkie Pie would deliberately lose everything then kibitz over everyone’s shoulders the rest of the game.

Don’t forget Risk

never play monopoly when you are a guest to someone else. They’ll have a ton of custom rules to make things more interesting, and you’ll know none of them, making you a bloody noob.