Definitely Wolverine and Deadpool. They have a lot in common, like their regenerative abilities and their combat skills. Their interactions could be really interesting, with Wolverine being all serious and Deadpool cracking jokes all the time.
Probably Wolverine and Spiderman. Wolverine is often on the front lines in X - Men stories, and his no - nonsense attitude would contrast well with Spiderman's quippy nature. They might meet when investigating a strange occurrence in New York that involves both mutants and non - mutants.
Sasuke and Magneto. Both are complex characters with a bit of a dark side. They could either become enemies as their goals might clash. Sasuke is on a journey to gain power for revenge, and Magneto wants to protect mutants but sometimes uses extreme methods. Or they could form an unlikely alliance, learning from each other's determination and power - seeking motives.
Mercy from Overwatch and Cortana from Halo might have an interesting interaction. Mercy is a healer and Cortana is an AI. They could discuss the ethics of artificial intelligence and how Mercy's healing technology could potentially be applied in the Halo universe, or vice versa how Cortana's knowledge could enhance Overwatch's medical technology.
Issei would be very likely. Since Issei is the main character in DxD, his curiosity and his own pursuit of power would make him interested in Goku. They could train together and learn from each other's abilities. Also, Rias would interact with Goku. As a powerful devil, she would be intrigued by Goku's power and his different way of approaching battles.
Yang would be a likely character. She's bold and not one to back down from a challenge. She might see Godzilla as a huge opponent to test her strength against. Maybe she'd start off trying to punch it, only to realize that brute force alone won't work and then have to figure out a more strategic way to interact with it.
Jade West from 'Victorious' and Stef from 'The Fosters' might also be a great pair to interact. Jade is tough and outspoken, and Stef is a strong - willed woman. They could start off butting heads but then find common ground and respect for each other. Maybe they both have to deal with some kind of troublemaker in their respective communities and end up sharing strategies.
Sunset Shimmer and Sonic might be the first to interact. Sunset has a bit of an edgy side and Sonic is always ready for action. If Sonic showed up in their world, Sunset would probably be the one to confront him, thinking he's a threat. But as Sonic explains his situation, they could start to form an alliance. Also, Sunset has experience with different worlds and magic, which could be useful in helping Sonic navigate the Equestria Girls' world.
Deadpool and Wolverine are a great pair. Wolverine's serious and no - nonsense attitude contrasts perfectly with Deadpool's zany and irreverent personality. They could have some epic battles where Deadpool's constant chatter drives Wolverine crazy, but also some moments where they realize they're not so different. Another good pair would be Deadpool and Rogue. Rogue's power - absorption ability could lead to some interesting situations when she tries to touch Deadpool, and his unpredictable nature would keep her on her toes.
I think Quinn and Black Widow would be an interesting pair. Quinn is used to being in a position of power and popularity in the Glee club, and Black Widow is a strong female character in the Avengers. They could have some really cool exchanges about strength and femininity.
I think Sakura from Naruto and Stella from Winx could interact a lot. Sakura is a strong - willed and intelligent kunoichi, and Stella is a confident and powerful fairy. They could have some really interesting conversations about their respective worlds, like comparing the medical ninjutsu in Naruto's world to the healing magic in the Winx world. And they might also get into some friendly rivalries while training together.