For me it's a tie between Discord and the Changeling queen.

Nightmare Moon -

Powers: Miscellaneous Alicorn powers, control of the moon and stars, transformation. 7/10
Evil act: Creating eternal night for all of Equestria. 8/10
Motivation: Revenge and spite for being imprisoned by her own sister. 7/10
Style: Tall, loud, threatening, condescending. 8/10
Defeat: Friendship'd into former self in one blow. 7/10
Conclusion: A classically designed and executed antagonist.

Discord, God of Chaos -

Powers: Manipulation of time and space, mind control, anything. ?/10
Evil act: Creating eternal chaos and unrest for Equestria. 8/10
Motivation: It's in his nature, revenge? 6/10
Style: Manipulative and condescending, but playful and nonthreatening. 6/10
Defeat: Friendship'd into stone after one failed attempt. 8/10
Conclusion: Though powerful, he remains short of being a genuine threat.

Chrysalis, Queen of the Changelings -

Powers: Transformation, miscellaneous alicorn powers, mind control, an massive army. 10/10
Evil act: Kidnapping royalty, capturing an entire country, creating chaos. 10/10
Motivation: Food for her kingdom. 3/10
Style: Manipulative, covert, threatening, pure evil. 9/10
Defeat: Delayed the Elements of Harmony, but was sent blasting off again by the power of love. 9/10
Conclusion: An amazingly intimidating enemy with a understandable motive.

Nightmare Moon is the most capable, Discord is the most powerful, and Chrysalis is the most evil.