Game with Most Difficult CPUs?

[DarkDesertFox]

Yup, for me it would be Sonic Shuffle. The NPCs always know which number card you have that they need and will take it from you to reach the precious stone or some other goal they have in mind. Furthermore, they are masters of mini games. For instance, the computer players put up a good fight in the snake jump roping mini game to the point they can beat humans regularly. Putting them on hard difficulty is like playing against the devil. Which CPUs cause the biggest trouble for you?​

 

[saehanfox]

Almost every Mario spinoff game that's not Mario Kart. In Mario Hoops 3-on-3, the AI is practically unbeatable in the final cup of hard mode. In Mario Strikers Charged, the AI in the final rounds are brutal and taunt you. In Super Smash Bros 4 Wii U, they can be untouchable in intense mode.

 

[Alienfish]

Haha, I didn't find Shuffle that annoying, each to their own though.

However, I'd say Hyperdevotion Noire: Goddess Black Heart. Most of the characters as bosses are way too OP unless you have luck or re-do it on easy mode.

Civ V if you play on 5 or higher.