For those that haven't played the game (I haven't read the manga so I don't know if it's the same there), Karol and Nan are a pair of kids who grew up in a city of guilds. At some point as they grew up Karol started having trouble keeping up, lost confidence, and started to become cowardly, giving up and running away at the slightest challenge. Nan seems to have tried to support him for a while, but a combination of her already hard attitude and frustration at his continuing to abandon friends to save his own skin, she herself rejected him and showed some real contempt toward him. He later met the main group and started travelling with them, and his experiences with them combined with his memories of his past failings gradually lead him to grow and change, eventually becoming a truly strong and brave fighter who will jump straight into a monster's open mouth to save a friend; he even saves Nan on multiple occasions, and in some of the potential sidequests she becomes very impressed with him, and shows a lot of previously unseen sides of herself, even breaking down in one case over the fact that he'd push himself so far, and giving some clear indications that she's in love with him.

So, what I want is, a pair of childhood friends who at first were very close and together pursued some lofty goal. However, due to differences in power, personal failings and other factors, the girl becomes disillusioned with the boy and leaves him or pushes him away, maybe out of anger at his failings, maybe contempt at his weakness, maybe just a desire to push him out of a job that's too dangerous for him. The boy doesn't give up though, and continues to try and change, eventually finding a new place where he's able to truly grow and advance. The two meet up later, and every meeting has a lot of uncertainty on both sides, especially the girl who sees him having becomes something completely different than he had been.

Extra bonus if they don't just run into each other, but actually wind up together again. Like, if the girl somehow ends up joining the boy's party/guild after he'd managed to grow and make something of himself there.

Closest I know of that approaches this is [m]Hazure Skill [Mapping] wo Te ni Shita Shonen ha Saikyou Party to Dungeon ni Idomu[/m], which starts out with the hero adventuring with his childhood friend but having no confidence in himself due to his "worthless" skill and really slacking off, until she and he part ways, and then he ends up meeting the most famous adventuring party, who see a legitimately crucial value to his skill. While the beginning matches up well with the beginning of the relationship dynamic I'm looking for, I haven't read far in the manga, not at all in the light novel, and so I don't even know if he ever sees the girl again, much less how things may be when/if they do meet back up and she manages to see how he changed. On a side note, if anyone is up to date with that manga (or better yet, the light or web novels), feel free to post or message me if the girl in question does indeed become a part of the story and not just a face in the flashbacks.