Disney+'s Loki series throws the titular villain thrown into the time-traveling, multiversal bureaucracy of the Time Variance Authority. Founded by the Time-Keepers, this infinite organization keeps tabs on all events across the Marvel Multiverse. While Loki will be working with the T.V.A. to ensure that the timeline remains as it should be in the MCU, the Time-Keepers have been at the heart of some devastating plots in comics, the worst of which almost broke up the Avengers as soon as they had formed.
In 1963's Avengers #2 by Stan Lee and Jack Kirby, the Marvel heroes were attacked by what appeared at first to be one another. Tensions had already been growing high between the Mighty Thor and the Incredible Hulk, so when the two finally came to blows it was no real surprise. However, this violence was revealed to be a ploy by the Space Phantom to tear the team apart. This mysterious villain had proclaimed that he was clearing the way for his people's invasion of Earth by copying the powers of the Avengers and subsequently banishing them to Limbo. Years later, this seemingly simple plot would have its layers peeled back to reveal the dark secret that had been hiding at the center of it all along.
Nearly four decades after their second adventure, a huge part of the Avengers' secret history was revealed in the pages of 1999's Avengers: Forever #8 by Kurt Busiek, Roger Stern and Carlos Pacheco. In a story that brought together Avengers members from several eras, a fit of rage on Hawkeye's part forces the Space Phantom to reveal his presence as an inanimate object hiding amongst them as they hurtle through time itself. It doesn't take much convincing to get the Space Phantom to tell them everything he knows, and it all starts with Immortus., the future version of Kang the Conqueror.
This evil Nathaniel Richards from the far away future was at some point visited by the Time-Keeperse. With his army of beings who had been twisted into Space Phantoms by their extended stay in Immortus' Limbo, the villain set into motion multiple attempts to keep the Avengers from staying together if not eradicate them entirely, all at the behest of the Time-Keepers themselves.
As far as the Time-Keepers were concerned, the Avengers' continued interference and influence of major historical events on Earth and beyond made them far too dangerous to the timeline as a whole. Not only was there the potential for Earth's Mightiest Heroes to have too great of sway over the course of its future, but the existence of numerous futures in which they had become threats unto themselves left the Time-Keepers with seemingly no choice but to interfere.
Thankfully, the Avengers managed to defeat the Space Phantoms and Immortus at every turn that mattered, and the Marvel Universe has been far better off for it. While the Time-Keepers and the TVA might not be the most famous names in Marvel history, moments like this show just how deeply they're intertwined with the Marvel Universe.