Agents of SHIELD is full of interesting and unique characters, and since the show is based on the titular organization from Marvel comics, lots of the elements of the series are taken directly from the source material. However, while some characters like Agent Mack or Daisy Johnson are based on pre-existing characters from Marvel, others were created solely for the purposes of the series.
Coming up with original characters often gives the writers more creative freedom, which is a large part of the reason why most of the originals have gone on to become fan-favorites.
Phil Coulson
The main character of the series is Clark Gregg's Agent Philip Coulson. Based on the overwhelmingly positive reception the character received when he was first introduced in Iron Man, it is kind of surprising that the character wasn't one that existed before the MCU.
He has later been written into the comics thanks to the success of the character in live-action.
Fitz and Simmons
On the show, Agents Jemma Simmons and Leopold Fitz are members of Coulson's original crew, the former as a biochemist and the latter as an engineer.
They were practically inseparable, with them even getting married in the show's 5th season and having a child together in the 7th. They were both eventually added to the comics "S.H.I.E.L.D. #1" in 2015, but their relationship there is much different than how it's portrayed on the show.
Melinda May
Agent Melinda May was a former field agent who was working desk duty and was directly asked by Coulson to fly the new team's plane, commonly referred to as the Bus.
As the seasons went on, she became to be more involved in the field, and sacrificed her life defending the team before being brought back. She would be introduced to the 616 universe in the same comic that first debuted Simmons and Fitz, where she is still a member of Coulson's team.
Grant Ward
Agent Grant Ward is one of the original members of Coulson's team who turned out to be working as a double agent for Hydra. Ward would eventually be killed by Agent Coulson and possessed by the ancient Inhuman, Hive.
While the character made his debut in the series, he was later added to the comics as a villain that went by the name "Iron Thief" who uses an Iron Man armor and acts as a sometimes-ally, sometimes-enemy of Agent Coulson, largely reflecting his role in the MCU.
Lincoln Campbell
When Daisy went to Afterlife following her receiving her powers, she met a lot of different Inhumans, one of them being Lincoln Campbell. Lincoln was a follower of Jaiying, with the ability to generate and manipulate electricity.
After helping prevent a war between Inhumans and humans, he became a SHIELD agent, Daisy's boyfriend, and a member of the secret warriors, which would lead to him sacrificing himself to stop Hive in season 3.
Joey Gutierrez
Another original inhuman created for the show was Joey Gutierrez. He received his powers from fish oil pills that he took during the Inhuman Outbreak, which caused him to have the ability to manipulate metal.
After being rescued from the ATCU by SHIELD, he would eventually go on to be an agent and join their task force known as the secret warriors.
Antoine Triplett
Agent Antoine Triplett is the grandson of one of the Howling Commandos that joins Coulson's team after his Superior, John Garrett, is arrested for working with Hydra.
Tripp was a member of the team for only one season before he was killed while trying to save Daisy and finding himself trapped in the Kree City.
Daniel Sousa
First introduced on Agent Carter, Agent Daniel Sousa was a veteran that worked with the SSR and was in a relationship with Peggy Carter.
On SHIELD, he was rescued by the team before what was supposed to be his death, where he would then start a new romantic relationship, this time with Daisy Johnson. After the core group split, he and Daisy would go into space and continue to work for the organization.
Raina
Raina was a main antagonist in season 1 who became obsessed with going through the process of Terrigenesis after being told by her grandmother that it was in her destiny to go through the mists and become something beautiful.
She and Daisy ended up trapped in the ancient Kree city, and both got their powers at the same time. While she gained enhanced strength and the ability to see the future, her skin also became spiked and dangerous, which made her hate her appearance.
Enoch
Enoch was a member of the Chronicoms, an alien race of synthetic humanoid-robots, that was tasked with observing Earth. However, when he learned of the Earth's near extinction, he would then capture the SHIELD team and send them to the future to help them deal with the threat.
He went on to become an ally of the team, even sacrificing himself to free them from a time loop in the final season. While the Chronicoms are original creations for the shows, they seem incredibly similar to that of the Watchers from Marvel comics.
Deke Shaw
At the start of season 5, the team traveled to the year 2091 where they first met Deke Shaw, a scavenger who lived in the Lighthouse, which was attached to one of the last remaining pieces of Earth.
After the crew returned to the present, and Deke along with them, it was revealed that he was actually the grandson of Agents Fitz and Simmons. This revelation led to a major shift in their dynamic and how Deke was viewed by the rest of the team. It also meant him desperately trying to keep them both alive to ensure his own future.