Apocalypse and his Horsemen
Apocalypse leads his Horsemen to enforce his 'survivor of the fittest' philosophy.
The Hellfire Club is a respectable, upper-class social organization with an Inner Circle whose subversive members engage in a conspiracy to dominate the world through the accumulation of economic power and political power. For a long time, the Inner Circle is comprised mainly of mutants. Recently, human billionaire Kade Kilgore took over as Black King with the Inner Circle now a mutant-hating organization.
The Hellfire Academy is set up by the Hellfire Club Black King Kade Kilgore as a rival to Wolverine's Jean Grey School for Higher Learning. The students of the Academy form the New Hellions team.
Over the years, the X-Men faced a number of threats who want mutantkind exterminated.
Sentinels, giant killer robots
Nimrod, advanced Sentinel from the future
Bastion, merged form of Nimrod and Master Mold
William Stryker, religious fanatic who employs the mutant-killing Purifiers
Bolivar Trask, creator of the Sentinels who heads the Mutant Response Division after his resurrection
Steven Lang, head of Project Armaggedon
Cameron Hodge, leader of the mutant-hunting Right
Donald Pierce, leader of the cyborg Reavers
Graydon Creed, politician and leader of the Friends of Humanity
Leper Queen, leader of the mutant-hunting Sapiens League
Hellfire Cult, a mutant-hating group created by the mutant Empath
U-Men, a group of humans who grafted mutant body parts onto themselves to become the third species