The middle of Season 1, when Amy explains to Shane why she can't tell Karma she's fallen for her.
Amy: She's been my best friend since kindergarten. If I tell her, things will get weird. And we'll drift apart, until one day we'll meet in line at the grocery store, and say polite hellos and... pretend like we didn't once know everything there was to know about each other.
In the Season 1 finale: "Amy, do you have feelings for me?" and everything that proceeds from there. If you pay attention you can spot the exact moment Amy's heart and given the ending of the episode possibly her sanity shatters into a thousand or so pieces. Right after "I slept with Liam".
Made worse that Amy had convinced herself that Karma felt the same way about her that she feels for Karma.
The end of 2x08, when Liam reveals to Karma that he "slept with someone".
Karma: Well, it's not like you slept with someone I know...*Liam makes sad face*...it's not like you slept with Amy...*Liam makes worse face, Karma realizes and pulls away.* Get. Out.
In 2x13, Amy breaks up with Reagan because they both know they're going in different life directions.
Shane's attempt to win Duke back with an apology ends with Duke leaving for his career, finally showing Shane how much he screwed this up. And this is after he spent the episode crying in detention about it.
The final Karmy scene of season 2B, where Amy is about to leave for the summer to spend the longest time away from Karma that she's ever been, and Karma tries to stop her:
Karma: What do I have to do to get you to stay?
Amy: You can tell me that that kiss meant something.
Karma: (breaking down) I can't.
Amy: (trying not to break down herself) Have a good summer, Karma.
The end of Karmygeddon (S3E3), where Amy admits she's not totally over Karma, and Karma admits that she misses being the center of Amy's world. Set to "Girls Just Wanna Have Fun", just like the first Karmy kiss.
