Jesse's motivations. He was almost completely ignored after Kate was diagnosed and Anna was born because he wasn't a match for Kate, and ended up destroying things because he'd never been able to fix them.
Anna's entire situation, being dehumanised by your own mother because she expects you to sacrifice your wellbeing to save your sister. It's worse in some ways for Jesse; since he's not a compatible donor, he's often pushed aside completely.
Good god, the ending. It's especially heartbreaking because just before the accident, Anna had indicated that she intended to give Kate a kidney (the difference being that now it's her decision to make, not her parents'). Kate ends up surviving and going into remission from the transplant, which suggests that if not for the accident, Anna and Kate could both have lived.
Sara breaking down in front of Kate and Anna's narration telling us that Kate died that night.
Kate choosing to die from cancer than witness her family emotionally torture her younger sister into giving up a kidney and further expect her to essentially sacrifice her future for her.