Neo could be going up against a fellow human in The Matrix 4, rather than the Machines and Agents of the original trilogy. When The Matrix began in 1999, the Wachowskis crafted a classic science fiction tale of man versus machine. Humankind had been overtaken by its own mechanical creations and placated in an alternate reality that was policed by the ruthless Agents, the most sinister digital creations since Microsoft first introduced Clippy. While the last bastion of humanity stands against the Machines, Neo makes a deal with their enemies to take down Agent Smith, who has now become a threat to both races. By sacrificing himself to destroy Smith, Neo creates a world where Machines and humans can, in theory, coexist.
With The Matrix 4 due to land in 2021, that fragile peace looks destined to be broken. Keanu Reeves' Neo and Carrie-Anne Moss' Trinity will be returning for the upcoming sequel and be forced to deal with an as-yet-unknown threat. Most would logically assume that whatever balance was created by Neo's death has somehow been lost - the Machines have risen up again to oppress their fleshy creators. Alternatively, perhaps Agent Smith has been revived from the dead. Hugo Weaving's villain always was a slippery customer, and the actor himself confirmed an offer to return for The Matrix 4 was made.
However, both of these avenues feel well-trodden. After three movies of humans fighting technology, a fourth would have to work hard to break new ground with the same concept. Reviving the Zion vs. Machines war may also undermine the conclusion to the original Matrix trilogy, with Neo's big moment feeling rather pointless if the same old rivalry stoked up once again. To prevent The Matrix 4 feeling stale, Neo could face off against an entirely human villain - a threat that comes from within, rather than the intangible Agents or the unfeeling Machines.
In the world of The Matrix, those hooked up to the simulated world are given the choice between a red and a blue pill. Those who choose the blue flavor are allowed to continue their blissful ignorance inside the Matrix. Neo's breaking of the traditional Matrix cycle could be bad news for those blue pill takers just seeking a quiet life. This idea already exists in The Matrix thanks to the first movie's Cypher character, who betrayed his allies in exchange for being plugged back in. The Matrix Online even featured an entire cult based around Cypher's philosophy - the Cypherites. This sets up an undercurrent of human angst that could rise up and rebel against Neo's truce in the years following The Matrix Revolutions.
Another idea The Matrix 4's villain could incorporate is Dozer - the "natural" human from the original movie. Born in Zion, Dozer didn't have the ports necessary to plug into the Matrix, and in the post Revolutions landscape, his kind will surely become more common. Melding Dozer's biology with Cypher's attitude, The Matrix 4's villain could be a natural human who longs to be plugged into the Matrix and experience what they deem "true" freedom. Angry that their ancestors could exist in a digital reality, free from the pain and hardship of the real world, this new antagonist's goal would be to stoke tension between Zion and the Machines once again, restarting the war by force and reestablishing the Matrix as the method by which humanity is subjugated... for it's own good, of course.
The Matrix has always dabbled in a sense of duality, and a villain of this ilk would offer plenty. In the original trilogy Neo was the human fighting against the Machines. In The Matrix 4, the Machines may recognize that a new common enemy has appeared and digitally revive Neo as an avatar within the Matrix. In this scenario, the villain would represent humanity (albeit misguidedly) and Neo would be the digital creation, like Agent Smith in the initial run of movies but fighting for the side of good in The Matrix 4.
