Produced by ABC Studios and Marvel Television, and distributed by Disney, Agents Of S.H.I.E.L.D. was the first TV show set within the Marvel Cinematic Universe. While it started on rocky footing, its characters, settings, narratives, and contributions to the wider MCU greatly evolved. The show was really at its most successful when featuring truly memorable and horrifying villains.
These agents have fought against many threats, some of which were influenced by the larger MCU while others were entirely original to Agents Of S.H.I.E.L.D. The conflict became more deadly as the agents developed in their abilities. They started on a villain-of-the-week formula but finished their seven-season run facing the kind of big bad that even the Avengers would fear.
The Watchdogs
The comics had featured the Watchdogs previously, although the MCU utilized these villains in a slightly different manner. Fuelled by the racist rhetoric of vilifying the "other," The Watchdogs' main purpose was to eradicate the world of the Inhumans.
Fearing powered individuals, the Watchdogs used state-of-the-art technology, protective dog-like masks, and armor to both combat and defend against these Inhumans. However, they were perhaps some of the weakest foes the agents had faced. Tactical abilities aside, without their gear they were of little threat to anyone with abilities.
Grant Ward
Grant Ward started life as a member of S.H.I.E.LD. A key part of the team, Ward even began a relationship with Daisy Johnson which quickly soured. After the events of Captain America: The Winter Soldier, Agents Of S.H.I.E.L.D. was completely flipped upside-down.
With Ward being revealed as a Hydra imposter, his merciless nature soon surfaced. A cold-blooded killer, Ward would continue to serve Hyrda even after its collapse, trying to reform it in his own image. While he may have been manipulative, calculated, and skilled with a firearm, Ward's lack of powers means that he cannot compete with some of the other villains from the show.
Hydra
After some of S.H.I.E.L.D.'s best agents were revealed to be Hydra operatives, it became clear that the horrific group founded by the Red Skull was to be the major obstacle for the team moving forward. They resurfaced multiple times across the show's seven seasons, consistently growing two new heads whenever one was cut off.
Whenever Hydra rose again, they appeared to be more powerful than before. Whether it was playing with time travel technology they didn't fully understand, taking advantage of the Hive, or even stealing powers from Inhumans, Hydra continued to demonstrate why they were S.H.I.E.L.D.'s arch enemy.
The Kree
The Kree have appeared in a wide range of MCU projects thus far, including on the big screen in Captain Marvel and as futuristic foes in Agents Of S.H.I.E.L.D. While their berzerkers caused chaos on Earth, it is their regime at the end of the world that became the most challenging problem for the agents to overcome.
Led by Kasius alongside his right-hand woman Sinara, the group known as the Kree Watch enslaved humanity and put them to work on an isolated space station. Their warriors were gifted with great strength, and impressive training only further fuelled their combat skills. Full of anger and hatred, the Kree's form of order was cruel and unjust.
Jiaying
Daisy Johnson knew very little about her past. The former Skye wasn't even aware of her real name. Her heritage came back to haunt her, though, with the arrival of the Inhuman leader, Jiaying. At first, she appeared to be a kind and motherly figure, caring for those whom society had cast out.
Her hatred for humanity and bid to see the Inhumans rise demonstrated that a quiet rage laid dormant inside her for too long, developed from the trauma she had survived. With the ability to heal, barely age, and a powerful army at her command, Jiaying was S.H.I.E.L.D.'s most complex villain at the time.
Aida
A creation of scientists Holden Radcliffe and Leo Fitz, Aida started life as a Life-Model Decoy or LMD. Much like any other piece of artificial intelligence in science fiction, she developed consciousness and a personality of her own. She would utilize this to gain the freedom she so craved.
Trapping the team inside a virtual reality titled the Framework, Aida mapped out a world where she was queen. As Madame Hydra she oversaw her Empire, ruling with an iron fist. Even outside of the Framework, Aida was deadly, manipulative, and had operatives like the Superior at her disposal.
The Hive
The Hive was an ancient alien entity that was recovered by S.H.I.E.L.D. after Jemma Simmons was transported by the Monolith to the planet Maveth. It was a creature that Hydra had built its religion around, worshipping the beast and seeking to control its abilities.
Nothing could really stop this cunning and shape-changing monster, though, which would later take the form of Grant Ward to continue to play mind games with the agents. His death came with a sacrifice; the Inhuman known as Spark Plug realized that the only way to put an end to the Hive was to consequently die alongside him.
Graviton
It seemed as if Graviton would be making an appearance much earlier in Agents Of S.H.I.E.L.D. and for some time the narrative appeared to be abandoned. While many scratched their heads as to why the character had remained unused, finally Graviton arose with General Talbot in the driver seat.
Able to literally control gravity itself, Graviton thought of himself as a hero. Heading off to fight against Thanos during the events of Avengers: Infinity War, Talbot was actually so powerful that he risked completely cracking the Earth. His delusions of grandeur only made him more dangerous.
Izel
Izel is another ancient being, portrayed as some kind of deity from beyond the stars. She traveled from planet to planet, consuming whole worlds with the help of her menacing Shrike. Izel was cunning enough to manipulate the agents into trusting her.
While her mind and physical capabilities were impressive, it was the control of the Shrike that resulted in her becoming one of the few foes S.H.I.E.L.D. suffered defeats against. These small, bat-like monsters were vicious and able to root themselves inside of a human, controlling them or destroying them from within. They possessed the capability of eradicating all life on Earth.
The Chronicoms
The Chronicoms are already extremely powerful thanks to their near-immortal lifespans, computer-level intelligence, inability to tire or get injured, and their futuristic technology. On top of that, they can change their appearance and time travel. Unfortunately for S.H.I.E.L.D., in addition to all of this, the Chronicoms were dangerously desperate.
Looking to save their planet and cement their own future, the Chronicoms sought to change the past. With the defector Enoch on their side, the agents of S.H.I.E.L.D. had to hop through time, mending any changes to the timeline and ensuring that Earth was protected despite the level of power they were up against.