Eredin (and the Wild Hunt) – While they are a bit underwhelming when Geralt finally fights them, they have so much menacing aura and influence over the main storyline/characters that it's hard to deny their impact. Plus, the armor design is impeccable.
The Ladies of the Wood – Also referred to as the Crones, the Ladies are an enigma in the swamps of Velen, saving some innocent folk in one breath while devouring their hapless children in another. While some argue their purpose is to look after and protect the people of Velen, it's made abundantly clear that they are monsters without remorse to Geralt and his friends.
Gaunter O'Dimm – Without out a doubt, one of the most well-written and terrifying antagonists in any video game I've played. He pops up as an unassuming NPC in the very beginning of the game, and weaves through the plot of the Hearts of Stone DLC like a demon straight out of old folklore. If you ever have the misfortune of meeting him, be careful what you wish for, lest he grant your wish.
Dettlaff – Also called the Beast of Beauclair, he is a member of the ancient race of Higher Vampires, monstrosities that are near impossible to kill. He is somewhat of a sympathetic figure for most of the Blood and Wine DLC, but is capable of immense savagery and cruelty when his emotions are brought to the surface. He is perhaps the most complex villain in the game, and arguably one of the hardest boss fights, if you choose to fight him.