The immense breakdown Twilight suffers throughout the story. It's pretty tragic seeing her become so psychologically broken due to the events of the wedding, but what makes it worse is the fact on that it was caused by her own best friends, her brother, and her own mentor.
Twilight's friends saying their goodbyes when she is given the choice to stay in Ponyville or start over in Canterlot.
Fluttershy appears to be taking her guilt over Twilight's condition the hardest.
Twilight crying while talking to the therapist is made worse when her own friends and brother overhear this and start to cry knowing they did this to her.
And Shining Armor becomes so ashamed of himself, that he resigns as captain of the guard.
When Twilight initially chooses to stay in Canterlot instead of returning to Ponyville, her friends are naturally dismayed by this, believing that their poor treatment drove her away. Fortunately, she reverses this decision.
Although this was changed when the writer added two endings: The first one being the original ending, where Twilight decides to go back with them to Ponyville despite her condition, or the newer ending where she does stay in Canterlot, but is determined to keep contact with the Mane Six always.
The only bittersweet nature of it all is Twilight reunites with Minuette, Lyra, Lemon Hearts, and Moondancer, her old group of friends from before the events of the series.
