The MCU and Supernatural both feature supernatural and fantasy elements in the forms of characters, events and worlds alike. It's not so far-fetched to think that there could be a possible connection between the two, which in turn would make romances between characters from these two universes that much more possible.
Sam and Monica Rambeau would certainly be a dynamic couple, supporting one another and everyone they come across in their adventures. However, Bela Talbot and Iron Man would be better off not knowing one another, given their morals are just too different for a relationship to work between them. Who else might work?
Would: Sam & Monica
Monica is a badass, and she cares for others. She was the only one willing to understand Wanda's pain and motivations in WandaVision, and she really connected with her as a result. Monica is also incredibly intelligent and kind. This isn't unlike Sam, who goes the extra mile to understand others, as was the case when he defended Amy and anytime he's defended Dean's actions. Together, Sam and Monica would be an unstoppable force, and they would be very caring and understanding towards one another, helping the other accomplish goals and still provide a listening ear whenever needed.
Wouldn't: Mary & Black Panther
Mary Winchester wasn't exactly mother of the year, especially since Dean and Sam found out she'd given Azazel permission to use Sam, and because she was so selfish and somewhat cruel upon being brought back to life by The Darkness. She failed to reconnect with her sons, and went off with the British Men of Letters. Where Mary put her struggles and needs above everyone else's, Black Panther is the exact opposite, as he is always concerned about Wakanda, and of course, his family, especially after the death of his father. Their goals and ideals are just too opposite for anything to ever work out between these two.
Would: Castiel & Captain America
Castiel is an angel of the Lord. Captain America is a famous soldier in America, a legend in the military. Both serve their leaders faithfully. Both men are dedicated to their posts. Castiel becomes more loyal to the Winchesters over time in the series, and even Captain America strays from authority, doing what he believes is right, especially in Captain America: Civil War.
These two men would certainly relate on their experiences in this sense, and they would make a striking team, with Cas in a trenchcoat and Captain America in red, white, and blue!
Wouldn't: Lucifer & Pepper
Pepper had a hard time accepting that Tony had become Iron Man; her reaction to Lucifer, not just to his powers and origin, but also his evil personality would be too much for her to comprehend. Lucifer happily tortures and kills; audiences will recall how he brutally killed Rowena, and how much he tortured Sam, especially in Season 7 of the show when poor Sam was suffering from hallucinations of Lucifer constantly. Lucifer never even cared for Kelly; he just wanted to use her to have a son of his own. Pepper wants a family and a future, and she loved how good Tony was; given her taste in men, she'd be horrified with Lucifer and would want nothing to do with him.
Would: Charlie & Jane Foster
Charlie is down for anything, whether it be research or an adventure to Oz with Dorothy herself. Jane is the same way; she's dedicated to her work and even got to go to Asgard. Both women are incredibly smart, and resourceful. They know how to handle themselves, and they both happened to get whisked into the world of the supernatural unintentionally. However, both took it on, with Charlie helping the Winchesters and Jane helping Thor. These two women would have a great relationship, and there would be nothing they couldn't tackle, especially if they were doing so together.
Wouldn't: Bela & Iron Man
Bela is sneaky, clever, smart, and only looks out for herself. Iron Man is eccentric, smart, sarcastic, and appoints himself as a protector of the world when he creates his suit. The two might have an initial attraction for one another because of their charms, but due to their very different goals and life choices, the two don't really have anything solid for a relationship. Bela and Iron Man would be constantly frustrated with one another.
Bela, because Iron Man puts everyone else before himself, and Iron Man because Bela only looks out for herself. She could never hang out with him or the Avengers, and he'd be thrown for a loop trying to understand her, given she double-crosses the Winchesters often and even made a demon deal in her past. They're better off as acquaintances, if anything.
Would: Sam & The Hulk
Sam and Bruce are more alike than meets the eye. Bruce struggles with his Hulk side, and Sam would likely relate given he has his own dark side consisting of demon blood and accompanying powers, courtesy of Azazel. Both men are wicked smart, given Sam is more inclined to do research on hunts rather than Dean, and Bruce can often be found in the lab, where he prefers to work alone, though Tony has helped him a few times.
Even though they have dark sides, both men are also incredibly sensitive and empathetic, as Sam demonstrates by helping the people he meets and Bruce does the same. They've both saved the world a few times, too, and would make one heck of an adorable couple!
Wouldn't: Dean & Black Widow
Yes, Dean and Natasha are very similar. They both have difficult backgrounds, they're both fighters, and they're both badasses. They're leaders, also. While similar, this is only a recipe for major clashing down the line. The two would constantly be engaged in a power struggle, and would likely be trying to one-up the other, especially Dean, given his competitive nature. Dean usually takes the lead and Sam allows it; Black Widow wouldn't be so inclined, and she'd fight Dean on it. They're better off respecting each other as colleagues or friends.
Would: Rowena & Loki
Rowena is no stranger to magic, and she's been known to double-cross not just the Winchesters, but also Crowley, her own son. Loki certainly has demonstrated his own magical capabilities in the MCU, and like Rowena, has stabbed his family (especially Thor) in the back a time or two. The two could relate on those levels; plus, both have been known to be good now and again, like with Rowena helping the Winchesters and Loki helping Thor escape from the Grandmaster.
They could share some laughs in their evildoing, and it'd be fun to see their dynamic as a couple.
Wouldn't: The Darkness & Thanos
The Darkness, aka Amara, was the main villain in Supernatural throughout the eleventh season, and she was shown to have quite the grudge against her brother, who happened to be Chuck, aka God. Thanos is one of the most dangerous and well-known villains in the MCU. Their similarities end there. Amara's motivations are completely different from Thanos's, in that she really just wanted her brother back and to be freed. Thanos thought he was doing the universe a favor in eradicating half the population upon several planets. Their manners of thinking and goal-achieving are just too different, and the two would likely rather destroy than love one another.