Despair

"It's true that I've saved a few people, but in equal measure, my heart became filled with resentment and hatred. So much so that I even hurt my dearest friend. For as much happiness as we wish on one person, we can't help but curse someone else. That's how it works for us magical girls." — Sayaka to KyoukoAfter analyzing all of the timelines in which Sayaka despairs, I feel there are two main themes that contribute to her losing sight of what is important: her loss of humanity and inability to deal with difficult emotions.
Loss of Humanity

Sayaka's feelings for herself after finding out the truth about her body are made apparent during her fight with the witch Elsa Maria. She battles the witch recklessly by charging forward without thinking, allows herself to be severely injured and expends a great deal of magical energy without second thought. She even declines Kyouko's help and coldly insists on doing it herself. Despite bleeding profusely from various parts of her body, Sayaka laughs and comments on how Kyuubey was right—she really doesn't feel any pain if she cuts herself off from her body. To be honest, she looks like she's completely snapped and went crazy during this scene the way she hacks at Elsa Maria and laughs maniacally. Madoka and Kyouko watch in horror as Sayaka pushes her body past its limit. She felt as though she was already dead, so why did it matter that her body was being injured? It's not like she felt pain anymore, anyway. If this scene doesn't depict her disgust and disregard for herself, I'm not sure what else would.
In addition to feeling like a monster, Sayaka's struggle around her loss of humanity also includes feeling like she has nowhere she belongs. She feels she has no right to try to win Kyousuke back from Hitomi because she's already dead. She has no right to interact with normal people or live a normal life because she isn't normal. She can't date anyone. She can't expect that anyone would want to be friends with her if they really knew what she was. Sayaka feels like she isn't needed by anyone and desperately wants to be accepted and feel like she belongs somewhere—belongs with someone. If she can't accept herself, who would? I think part of the reason she pushes Madoka away and gets angry at her undeservingly is because part of her feels there's no way Madoka could really care about her the way she is. Madoka won't become a magical girl knowing what happens to their body. If Madoka rejects becoming a magical girl, then she is basically rejecting Sayaka, too. Already feeling like she is a monster with nowhere she belongs, Sayaka snaps and projects her own feelings onto Madoka. Sayaka's struggle with her loss of humanity and subsequent hatred for herself cloud the way she thinks others view her. Feeling isolated and alone makes life hardly worth living, especially considering she made a wish based on a relationship with another person. I think this perception causes Sayaka to begin losing sight of what's important.
Difficult Emotions

Sayaka also struggles with her feelings around Kyousuke and Hitomi beyond just wishing Hitomi wasn't in the picture. She feels as if Hitomi is stealing Kyousuke away from her and that there is nothing she can do about it. Sayaka is stuck between a rock and a hard place, basically. She tells herself she can't be with Kyousuke the way she is due to her losing her humanity, but she also can't give them her blessing either. There's nothing she can do but let Hitomi take Kyousuke from her and drown in her feelings of jealousy, resentment and regret. The anime does a wonderful job of representing this by switching between Sayaka watching Hitomi confess to Kyousuke with her basically rage fighting and symbolically losing herself in her overwhelming emotions. Feeling cornered also triggers Sayaka's ideals around justice because she can't watch over them when they are together. She doesn't want to protect them knowing they are together. In the PSP game, Kyouko actually has to ask her if Kyousuke is no longer worth protecting and fighting for just because he's dating Hitomi. Sayaka realizes she is being silly but her resolve still falters the second she sees them together. Not wanting to protect someone also violates what she believes a magical girl should be and therefore she perceives herself as a failure once again.
Further, I think Kyousuke accepting Hitomi's feelings also leads to Sayaka struggling to understand her own feelings for him. She feels like an idiot for thinking there was something between them and is upset that he didn't seem to realize her feelings for him. Though not directly stated, I personally believe the scene on the train before Sayaka turns into a witch is her processing her hurt and angry feelings toward Kyousuke. She overhears two men completely trashing a woman. Sayaka asks him if he realizes that she was probably in love with him and works hard to make him happy. She deduces that the man probably already knew this, never said thank you to her and now wants to get rid of her because she is no longer useful. Sayaka spent a lot of time and effort caring for Kyousuke when he was in the hospital. As soon as he was released and went back to school, however, he didn't reach out to her at all. Although the situation isn't that black and white based on the hospital changing their relationship dynamic, it seems Sayaka perceives that Kyousuke threw her away because he didn't need her anymore. Sayaka wonders out loud if the world is even worth protecting and about what she has been fighting for this whole time—representing her losing sight of why she became a magical girl to begin with. Feeling angry and hurt, Sayaka's original wish to hear Kyousuke play violin again becomes clouded and she regrets her decision to heal his hands. Making his dream come true was no longer worth the fate of a magical girl.
One last difficult emotion that Sayaka struggles with is guilt. Depending on the timeline, the source of her guilt varies. Sources include the previously discussed guilt over wishing Hitomi were dead and not wanting to protect her or Kyousuke anymore, feeling guilty over Mami's death and/or letting Mami down because she is a failure as a defender of justice, saying terrible things to Madoka and Homura and feeling like she has been nothing but a burden to everyone. She feels weak, stupid, helpless and like a coward—all of which contribute to her being a perceived failure. This, too, leads to her feeling guilty. Guilt, compounded by feeling like an isolated monster who is a failure at being a magical girl and regretting her wish to heal Kyousuke's hands, ultimately results in Sayaka's inevitable transformation into a witch.
The Mermaid Witch

Oktavia's most notable feature is her mermaid tail. The mermaid witch likely represents Sayaka's association with water. However, I would argue that it could also symbolize parallels between Sayaka's story and the original The Little Mermaid story. The little mermaid agrees to have her tongue cut off and drink a potion that feels like a sword is cutting through her body in order to have human legs and win the love of a prince she loved. She also knows she will be unable to return to her life and the way she was before after becoming human. Even so, the little mermaid makes the contract with the sea witch and becomes human in exchange for her tongue. Unfortunately, the prince falls in love with another girl and the two get married. The little mermaid is heartbroken and despairs because she endured so much suffering in hopes of being together with the prince. She ends up turning into sea foam, which is what happens when mermaids die. I personally think that Sayaka's story resonates strongly with aspects of The Little Mermaid. Sayaka makes a contract with Kyuubey and becomes a magical girl—something that prevents her from returning to her old way of life. In exchange for her wish, she sacrifices her soul and humanity. Kyousuke, the boy she loves, ends up with another girl and she is heartbroken. Sayaka despairs because she suffered so much in exchange for her wish and dies as a witch. Making Oktavia a mermaid for this reason would be a perfect representation of Sayaka's despair, in my opinion!
b a c k . c l e a r . f o r w a r d Zero and its contents are © Samantha, however Sayaka and Puella Magi Madoka Magica are © Gen Urobuchi and other rightful owners. Zero is a part of SOUL-GEM.ORG.