Lucia route. Second least favorite character going into the route - favorite route of the VN.
I think that's very rare though. I either like the heroine, so I like the route, or I dislike the heroine, so I skip the route. If a character is just meh, I'll sit through the route for as long as it feels worthwhile, but it rarely ends on a positive note.
A lot of the VNs I've read don't really have heroine routes, so they all get disqualified immediately... It's been a long time since I last read a VN too, at least a year, so I'm probably forgetting a lot
Tsubaki's route from G-Senjou was a surprisingly fun read - all of the routes were.
Similarly, the only Sharin no Kuni character I liked was Ririko, but Natsumi and Sachi had good routes.
I'm not sure if Hisoka from Coμ counts. She was my favorite, but there were definitely times where I had to remind myself that~ It's a definite for Mayu-Mayu though. Wasn't expecting anything from her route, but it was fun.
I didn't like Rimu at the start of Deardrops, and there really wasn't anything that good about the VN, but I had a more positive outlook of her character by the end of the route.
I remember not liking Kudou in Da Capo, but god I spent a lot of time trying to get that route. It's been so long I don't even remember most of Da Capo outside of Kotori, Alice, Yoriko and Izumiko's basic plotlines, so I don't know if it was worth... but I spent a lot of time on it. (Nemu worst VN character ever?)
Anzu in DCII counts as well. Probably my favorite route - the most memorable at least. No pun intended.
Also foggy memories, but I remember the cast of Kazoku Keikaku taking time for me to like them.
Haruka in Litbus had a good route.
Disliked all of the main ShiniKiss characters at first, but I remember liking two of them by the end of it (that VN was a draaaag.)
Akira in Yosuga no Sora was a bundle of fun, but I hate those types of characters. The route was a bundle of fun though. (Nao worst VN character ever?.)
Everyone in The Second Reproduction. I think it's supposed to be that way though >.> It certainly knew it's target audience.
Nekoko and Aeka from Yume Miru Kusuri IIRC. Another oldie buried behind memories~ Didn't like the characters but boy those routes were... something. I only really remember the endings, but they were (terribly?) good endings.
I'd say some Cross Channel characters, but I don't even remember which parts were from which routes. Most of my joy in that VN involved the misery of characters I disliked... Haven't happily clicked choices like that since KOTOR, but you gotta stick with Youko man.
Kana ~Imouto~ comes to mind. I wish I could talk about that but... I don't remember a single thing about it, apart from IIRC it had a flashback with choices... which irritated me slightly.