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.
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.
Hulk might be an interesting one too. Sonic's speed could either annoy or amuse Hulk. If they end up on the same side, Sonic could use his speed to lead Hulk towards the enemies. And Hulk's raw strength could be something Sonic would be in awe of. They could have a really unique dynamic, like a fast - moving pest annoying a big, strong giant at first, but then they become an effective team.
It could be Zane from Ninjago and Trixie from Slugterra. Zane is very logical and has a lot of knowledge about technology and combat strategies. Trixie is smart and resourceful in the world of Slugterra. They might cross paths while investigating some strange occurrences that seem to be related to the crossover. Their initial meeting would probably involve a lot of questions and mutual curiosity as they try to figure out where the other is from and what they are doing in this new, combined situation.
Mercy from Overwatch and the Medic from TF2 could be the first to interact. Given their roles as healers, they would likely be interested in each other's medical techniques. They might start by comparing notes on how to heal their comrades more effectively, and this could lead to a deeper understanding and cooperation between the two groups.
In my opinion, it would probably be Kurt from Glee and Darren Criss (who is associated with Starkid). Kurt is very fashion - forward and has a strong passion for performing arts. Darren Criss is known for his incredible talent in Starkid productions. Their shared love for music and the stage would likely draw them together first.
Probably Leonardo from the Turtles and Freddy Fazbear. Leonardo is the leader, so he would likely be the first to step forward and assess the situation when they encounter the FNAF animatronics. Freddy, being the main animatronic, would also be in the forefront. Their personalities are quite different, with Leonardo being more disciplined and Freddy having a more mysterious and somewhat menacing presence. Their first interaction could be a tense stand - off as they try to figure out each other's intentions.
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.
Sonic and Natsu would be likely to interact first. Natsu is always eager for a challenge and when he sees Sonic's speed, he would be intrigued and want to test himself against Sonic.
Probably Bloom from the Winx Club and Master Chief from Halo. Bloom is the main character in the Winx Club, very powerful and often takes the lead in dangerous situations. Master Chief is the iconic figure in Halo. Their paths might cross first because they both have a strong sense of duty and leadership. They would be likely to recognize each other's capabilities quickly and start to work together, like when facing an initial threat that appears in both of their worlds.
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.