Agents of SHIELD season 6's main villain could be an escapee from Doctor Strange's Fear Dimension. Over the last few years, Marvel Television has essentially evolved into a superhero mystery show. Each season sets up a grand, overarching adventure-mystery for the SHIELD team to solve. Last season was all about working out what had destroyed the Earth and how to avert it. This season is all about the Coulson doppelganger and another potential extinction level event.
It's still unclear whether Sarge is an outright villain or an antihero who's willing to destroy entire planets and civilizations in order to destroy a greater threat. Whatever the truth, though, the threat he's trying to deal with is gradually taking shape. He's attempting to destroy a race of alien creatures known as the Shrike, who possess hosts and turn them into time-bombs to turn an entire world into fertilizer. The Shrike serve a mysterious "creator" - and in the latest episode, "Collision (Part I)", she finally arrives on Earth.
According to "Collision (Part I)", the Shrike's creator is an ancient - albeit humanoid - entity named Izel. Dr. Benson claims that thousands of years ago, Izel escaped "from a realm of fear and darkness." She made her way to Earth, and was incorporated into the mythology of the ancient Incas. Izel herself claims to have come from the same alien civilization who created the Monoliths, and she seems to have left Earth in order to hunt them down. Her precise goal is unclear, but it's presumably to use the Monoliths to transport herself somewhere. Ironically, what she doesn't know is that the Monoliths were destroyed in Agents of SHIELD season 5. After millennia of searching, she's finally about to return to Earth, only to find out she's too late.
Little by little, the pieces are falling into place. Back in season 5, the destruction of the three Monoliths created an unstable dimensional rift to a realm known variously as the Dimension of Dreams or the Fear Dimension. This is a classic idea from the comics, introduced in Strange Tales #110 - the same issue that introduced readers to Doctor Strange. Seeking to understand why a man's dreams were plagued with darkness, Strange waited till he slept, and actually entered his dreams. Even as he learned the truth, Strange found himself confronted by the master of the Dimension of Dreams, described as his "ancient foe," Nightmare. This proved to be popular with readers, and as a result Marvel Comics has returned to the Dimension of Dreams - and the Fear Dimension, which is linked to it - time and again. This sounds very similar to the place Izel escaped from, this "realm of fear and darkness."
It sounds as though the Monoliths are the key to all this. According to Izel, the Monoliths were created to connect life together; presumably to link time, space, and other dimensions. It's possible they were designed to be used in unison, to create the kind of interdimensional portals shown in Agents of SHIELD season 5. The Monoliths may well be how Izel escaped the Dimension of Dreams in the first place; it's unclear how she lost track of them, but they remained hidden on Earth, and centuries later one of them was used to banish the Inhuman Hive to the planet Maveth.
Assuming this theory is correct, it's surprising to see Agents of SHIELD revisit the Dimension of Dreams. The odds are good that this dimension will soon turn up on the big screen as well; Marvel Studios is finally moving ahead with Doctor Strange 2, and both writer C. Robert Cargill and director Scott Derrickson have openly discussed how much they'd like to use Nightmare, the lord of the Dimension of Dreams, as the villain. If the Dimension of Dreams is indeed returning, then Marvel TV is once again toying with ideas and concepts before the films have even begun to catch up.