Chris - Wesker Jill - Nemesis Leon - something in RE2 Claire - something in RE2 Sherry - Ustanak Jake - Ustanak Piers - Haos (obviously) Sheva - Wesker Carlos - Nemesis Steve - Alfred Barry - Wesker Rebecca - Marcus Billy - Marcus Ark - Hypnos Tyrant
Can't really say any of the enemies in RE4 gave Leon his biggest challenge. None of them really pursued him constantly and/or they were beaten the first time. Krauser got lucky he got in a strength battle, and I guess Mendez just kept getting the drop on him other than the first time Leon thought he could kick him, (lol). He only fought Ustanak once and he told Sherry Raccoon City was harder. Course it was one of his jokes, but it makes sense. He was a rookie after all. Maybe Mr. X was his biggest threat? Or Ada...
I'd say the same with Claire. Unless Alexia or Alfred takes the cake. She only has those two to judge from. Don't see nothing in Degeneration.
Chris - Wesker Jill - Nemesis Leon - Hair product shortages Claire - Trying to resist basementdude Sherry - Ustanak Jake - Ustanak Piers - Haos (obviously) Sheva - Wesker Carlos - Nemesis Steve - Alfred Barry - Wesker Rebecca - Marcus Billy - Marcus Ark - Hypnos Tyrant
Ada is Leon's biggest threat. Despite the fact the two love each other, the ***** always teases him and takes off. He can take on Tyrants, an entire cult possessed by parasites, survived three infected cities full of zombies and creatures, a war zone in the Eastern Slav, and took on the most annoying T-rex/quadrapedal feline creature of sorts/big ass fly boss hybrid ever. He still can't get the love of his life. Go figure.
I would say "G" was Claire's biggest threat, certainly more difficult than the plane Tyrant gave her. She had to climb under a moving train to just get away from it. Could also be Alexia too, since Alexia managed to capture Claire and Steve. Chris was the only reason she survived that encounter.
As for Leon... I dunno. Trenchy wasn't all that difficult because he didn't run until his coat was burnt off. By that time, a single rocket was all it took. I would actually list Trency as Ada's biggest threat, since it wounded her throughout the game - nearly killing her the final time. He was certainly more trouble than Carla was for her.
I guess I would say Krauser would be Leon's. He managed to slice his cheek and would've gutted him if Ada hadn't saved him. During their final battle, Leon managed to knock him out long enough to grab the third emblem to escape being blown to pieces. But Ada's scenario revealed he survived the battle and explosion (with terrible burns} and she was the one that had to actually kill him - and only because he was in a crippled state.
"At times we must purge things from this world because they should not exist. Even if it means losing someone that you love" ~ Deadly Premonition
Leon had to deal with 2 mr X at the same time in Damnation, one of them pretty much hit him and kicked him in the ribs to send him flying. Same goes for Curtis when he turned into G beast, he sent Leon flying in one hit. If those two movies don't count, then there is also Javier that was about to kill Leon and Krauser if Manuella hadn't interferred.