In a word, everything. But if you want the details...
- Kate's crippling depression after Amelia dies. Kate was considering killing herself because Amelia is dead, but she doesn't, because she feels like she deserves to suffer and be punished for not preventing it. Which, in a way, is even worse.
- The actual death scene, narrated by Amelia."I tried so hard to hold on."
- The bullying Amelia undergoes after Zadie outs her against her will. Made even worse by the fact that Dylan abandons her and chooses to stick with Zadie.
- Reading the book, knowing what's going to happen.
- In a similar vein, re-reading the book and knowing the full story of what's going to happen. Dylan and Amelia's relationship and Amelia's fights with Sylvia come off as especially tragic in hindsight.
- The fact that Jeremy never got to tell Amelia that he's her father. Especially since, twisted and wrong as it was, his pretending to be Ben was motivated by a genuine desire to get to know her and connect with her.