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The Marvel Cinematic Universe is largely celebrated for its interconnected worlds, crossing over a vast amount of characters with each other. Fans saw the pinnacle of this in Avengers: Infinity War, which contained the largest number of main characters in any Marvel movie. Infinity War famously wiped the board clean in its epic ending, leaving plenty more room for other characters to share the spotlight. However, that doesn't mean that every major character is going to be in Avengers 4. Actually, there's a good chance that we see won't see certain characters ever again.
Not everybody gets to be as popular as Iron Man, Captain America, Black Widow, or Spider-Man. Plenty of characters have graced the big screen flying under the Marvel Studios banner and not all of them catch on with audiences. The reasons tend to vary but even Marvel has its misfires, and it's highly unlikely that any of these still alive, major, sides characters appear in Avengers 4.
One of the rare villains to make it out of his debut movie alive, Abomination might as well be good as dead. The monstrous villain hasn't been seen or heard of since The Incredible Hulk, which is pretty understandable. Given how the whole Edward Norton thing shook out, Marvel really wants to forget this movie exists. While there are certainly plenty of ways Abomination could be utilized in the future, this guy hasn't seen the light of day since 2008, so don't count on him showing up. Then again, it wouldn't be the first time that Marvel brought back an almost forgotten villain.
Thor: Ragnarok essentially ditched most of Thor's supporting cast in favor of a fresh start, and that included Jane Foster (Natalie Portman). Jane was never really able to escape the fact that she was a love interest, with much of her screen time spent pining for Thor. This got especially bad in Thor: The Dark World where she was a damsel in distress for over half of the movie. There were also reports that Portman wasn't too pleased with the production of the movie, meaning she was probably okay that she never got a callback. That being said, Marvel has changed a lot since those early days, and Portman has expressed a willingness to return if she were ever asked.
Another casualty of Marvel's selective memory when it comes to The Incredible Hulk. While her father General Ross has found new life in the MCU, Betty Ross (Liv Tyler) still lives in obscurity. Not even Bruce Banner has mentioned her name in 10 years, but there isn't exactly a high demand for her to return. Betty mostly existed as a way to emotionally ground the Hulk, but that role has partially gone to Black Widow (Scarlett Johansson), so Betty isn't too necessary these days. It'd be interesting to see her mostly just to find out what these Incredible Hulk characters have been up to.
This one might be a little unfair seeing as how her last appearance was just two years ago, but Doctor Strange didn't leave much open in the air for Christine (Rachel McAdams). The one-time lover of Stephen Strange is meant to be a representation of all that he will miss if he dedicates himself to the path of the mystic arts. Strange made his decision and thus there isn't anything for her to do anymore. If Jane Foster taught us anything, it's that people don't like characters who try to ground the more fantastical characters. Just let them be fantastical! It's hard to leave your mark as the normal character in a movie about reality protecting wizards, but Christine isn't a very memorable character.
Helen Cho's first and only appearance was in Avengers: Age of Ultron, in which she was introduced as a brilliant scientist who had developed a cutting-edge nano-technology. This tech is then used by Ultron to create Vision's body. Cho doesn't do much in the film, but there is a faint sense that she was partly meant to be a recurring minor character. This is partly bolstered by the fact that Cho is the mother of Amadeus Cho, one of the smartest people in the world who takes on the mantle of the Hulk for a time. Amadeus hasn't appeared in the MCU yet, so Helen might still have a future but it seems unlikely that Avengers 4 is on the table.
Talk about getting ahead of yourself. The Leader is one of the great hanging plot threads of the MCU. The villain was set up for a sequel to The Incredible Hulk that obviously never happened, leaving the character on the shelf to collect dust. The Leader is as smart as the Hulk is strong, but he still hasn't found a way to escape The Incredible Hulk. There's no chance that this guy, who didn't exactly light the world on fire, will factor at all into the events of Avengers 4.
Human characters have always had it rough in the Thor movies, but Darcy managed to be a slight exception to the rule. She was the comic relief back when the Thor franchise didn't have much of that to go around. Then Thor: Ragnarok was entirely comic relief and Darcy suddenly became harder to justify keeping around. While she definitely had her moments, Darcy could be pretty annoying at times. There's only so much snark someone can take from an intern.
This one actually hurts, but it's unlikely that Justin Hammer makes an appearance in Avengers 4. Justin Hammer doesn't rank particularly high on the list of Marvel villains, but the character is memorable thanks to the fun performance from Sam Rockwell. The last time we saw Hammer was in a Marvel one-shot (remember those?) where he was in prison and that's likely where he still is. One can only hope that he dances his way to Avengers 4, but he really didn't make that big of a splash in Iron Man 2. That's not to say he wouldn't make a fun Ant-Man villain, though.
If it was too hard to get Sif into Thor: Ragnarok then there's little chance she can get into Avengers 4. Leading up to the release of Ragnarok, there was a lot of buzz over whether Sif would be in the movie. Jaimie Alexander ultimately couldn't do it because of scheduling conflicts, but she probably lucked out considering every other notable Asgard side character was killed off. Sif is still out there in the galaxy somewhere, which means she's on the table for future MCU appearances, but like other Thor side characters, she's likely not a big priority.
As far as side characters go, Erik Selvig had a pretty good run. He got to be a science expert in both Thor and The Avengers, make a complete fool of himself in Thor: The Dark World, and then play a minor role in the least popular scene in Avenger: Age of Ultron. Selvig has been MIA ever since and while scientist characters are likely in hot demand to solve the Snap in Avengers 4, it feels like Selvig has run his course.
Trevor Slattery is one of the most controversial characters in the MCU. Billed as being classic Iron Man baddie the Mandarin, it turned out that he was just a dopey actor named Trevor Slattery in one of the best-executed plot twists in the MCU. It left fans divided to the point where Marvel had to make a one-shot explaining that Trevor wasn't the "real" Mandarin. It's that controversy amongst fans that will probably keep Trevor from showing up again, even though it'd be pretty funny that of all people, he ended up surviving Thanos' Snap.