The Infinity Stone have been repeatedly misused in the Avengers: Endgame. Before Thanos actively sought and eventually used them, however, the Infinity Stones have been used separately and in-tandem for different reasons — most of them were for not their original intended purposes.
The Infinity Stones had been in the MCU since the beginning of its known history, even if it didn't appear that way at first. For example, The Avengers, Loki's Scepter was also shown with no mention that it housed the Mind Stone. It took Marvel Studios a little while before they finally acknowledged that these mysterious gems were what they were presumed to be perhaps because they wanted to keep the overarching narrative of the Infinity Saga under wraps or this wasn't their plan at the beginning. Regardless, once their existence firmly established, the remaining stones popped up in varying films; only the Soul Stone was saved for Avengers: Infinity War when Thanos finally sought them himself.
Given this, some of the Infinity Stones had been wielded by different people and beings throughout the Infinity Saga. Since not much was known about them, they have been used incorrectly a surprising number of times, by both hero and villain alike.
The Space Stone Transports Red Skull
Formerly known as Johann Schmidt, Steve Rogers' first personal villain transformed into the Red Skull after using an imperfect replica of the Avengers: Infinity War when Thanos and Gamora traveled to the remote planet.
SHIELD Uses The Space Stone To Create Weapons
As the first Infinity Stone to factor into the MCU, the Tesseract had changed hands several times, including a stint with SHIELD. While searching for the missing Steve Rogers, Howard Stark retrieved the Space Stone at the bottom of the ocean, starting his and the organization's decade-long attempt to harness its powers. In the modern era, the World Security Council ordered the Nick Fury-led SHIELD to develop advanced weapons using the cube to better prepare Earth in case it's attacked by any extraterrestrial threats. Knowing the existence of aliens following his encounter with Carol Danvers, Skrulls, and Kree during the events of Captain Marvel, Fury led the program until this was discovered by the Avengers after Loki stole it in The Avengers.
The Reality Stone in Thor: The Dark World
After the Space and Mind Stones became prominent in MCU Phase 1, Marvel Studios Phase 2 continued introducing the Infinity Stones via the Reality Stone; which was called Aether in the film, as a result of its liquified form. Dark Elf Malekith wanted to use the Aether to plunge the Nine Realms into total darkness using an event known as the Convergence. The Asgardians were able to prevent this from happening the first time, but this didn't stop Malekith from attempting to do it thousands of years later during the next Convergence.
The Power Stone Kills the Collector's Servant
With three Infinity Stones already established in the MCU, the Collector's assistant, saw this as an opportunity to kill him, assuming that she could use the crystal to execute her nefarious plan. Without any hesitation, she grabbed the exposed Power Stone which quickly destroyed her body, effectively killing her.
The Mind Stone Creates the Twins
Like SHIELD, HYDRA also attempted to experiment on an Infinity Stone in hopes of using it to their benefit. Following The Avengers, Wolfgang von Strucker's cell was able to get a hold of the Scepter with the Mind Stone as revealed in Avengers: Endgame which they used to experiment on Wanda and Pietro Maximoff to give them powers. Marvel Studios may end up backtracking on this initial idea, though, as the explanation that the Mind Stone was the source of their powers was a way to retcon their mutant origins in the comics as kids of Magneto. Now, however, that the character rights of the X-Men are back to them, it seems the new explanation for the twins' powers is that they already had the X-genes, with the power of the Infinity Stone merely activating them.
The Mind Stone Creates Ultron
Once the Avengers re-acquired Loki's scepter from Hydra in Avengers: Age of Ultron, Tony Stark and Bruce Banner used it to move forward with Ultron Program which aimed to create an AI peacekeeping program. Unfortunately, their experimentation backfired after they attempted to harvest the net of neurons found inside the Mind Stone, which resulted in Ultron, the film's major antagonist. Granted that the pair used it again later in the film to create Vision, but the red Android was the result of the experimentation gone right, as he's dubbed the perfect form of Ultron.
Thanos Uses All Gems For The Snap
There's a reason why the Infinity Stones were scattered throughout the universe - to prevent any being from wielding their collective powers. However, Thanos was devoted to his goal to "balance" the universe. After he learned that there was a far quicker way to accomplish his mission with the use of the Infinity Stones, he started tracking them down. While Thanos justified his decision to wipe out half of the universe with the Stones as a brutal way to try and do "the right thing", it was in practice as Doctor Strange put it: genocide. Though Thanos' actions would eventually be undone, they are unquestionably the biggest misuse of the Infinity Stones to ever feature in the Marvel Cinematic Universe.
