A main character comes along once every thousand years, and Iihiko has defeated all of them, even Medaka. This millennium, however, there are two main characters...
Why does calm and rational Gagamaru explode with angerbeing told he only knows how to fight in childrens card games, even completely changing his normal demeanor and hairstyle? Because he reflexively shields himself from being hurt; physically, mentally, and emotionally with his Minus. The fact that Gagamaru got murderously angry is because he's unused to actually feeling hurt.
When Ajimu revives Zenkichi in chapter 71, she tells him that she's glad Zenkichi failed to kill Kumagawa as that means he isn't burdened with the karmic weight of Kumagawa's murder. Thirty chapters later, the reason why Ajimu wants Zenkichi to remain relatively innocent becomes obvious. This means that Ajimu may have been planning the upcoming confrontation between Zenkichi and Medaka the whole time.
One might wonder what ever happened to Zenkichi's own personal and much hyped skilll, Devil Style. In the arc after it's revealed Theory of Narrative Causality seems to be in full affect again when the heroes fight the suitors from the weakest to the strongest. That is until it's revealed that the first suitor, Nienami, is actually the strongest of the six.
Zenkichi's "Devil Style" sounds like a massive disadvantage, especially for one so underpowered in a world of over-the-top busted monsters. However, it's occasionally essential for his victory, because it also negates the otherwise inviolable narrative luck of other protagonists.
With the introduction of Iihiko, and the backstory of him repeated handing Ajimu her ass, it may seem odd when one thinks back to her motivation of challenging Medaka. After all, if Iihiko routinely beat her, why does she still feel like she always wins. It becomes more understandable if one considers it's been a few thousand years since they last met (admittedly a drop in the bucket of Ajimu's total life, but still). Thus, Ajimu's winning streak eventually reasserted itself over the millennia until she finally decided to go back to challenging the only thing that ever beat her: A Main Character. Of course, then she won, so it was back to the suicide. It helps that Iihiko never actually killed her, so it could be filed under the typical "main character get's beaten by this one super strong guy, but then totally gets stronger after coming back from the brink of death" cliche.
The finale of volume 16 and the Kurokami Medaka's Successor arc is an amazing callback. Ajimu deliberately crafted her planned end of the series to Bookend the beginning with an election, but it surpassed her expectations. Not only does Medaka lose, but she gets only 2% of the votes rather than all but 2%. It's Medaka herself that caps it off, though: Her grand "Life is Epic" speech to Ajimu? It's word-for-word identical to the end of her inauguration speech in chapter 1,note (the scanlators translated it differently) complete with wordplay on Ajimu's "Anshin'in" nickname! Given how early that nickname showed up, Nisio Isin had this ending planned for at least seven volumes.
When Medaka wrote up Ajimu's student information on her fan, she was copying Ajimu's "simulated reality" fourth-wall breaking. Only a reader of the comic would have recognized the student information boxes she mimicked, and she never turned the fan so Ajimu could see what she'd written. Parasite Seeing was one of the few skills Medaka knew Ajimu didn't have, so Ajimu couldn't see from Medaka's perspective. Holding that fan up like a caption would only benefit the reader...or someone who could see the world through the reader's eyes.
Fridge Horror: Kumagawa states that his All-Fiction won't let him truly die. The only way he could know this, and state it so confidently, is to have discovered it through experience.
Gagamaru goes right out and says that he's used his "Encounter" to push any mental trauma he might have had onto other people at random. Shibushi hints darkly that nobody knows what's happened to the people who had this trauma thrust upon them.
It could have all been pushed towards Kumagawa. That is one theory.
Gagamaru's relationship with Shibuki Shibushi becomes nightmarishly Squicktastic upon learning what his ability is, how it affects his personality, and for what reason she hangs around him.
Ajimu may have lost to Iihiko, but in that moment she defeated Medaka. Many readers and somehow Medaka herself may have forgotten, but Medaka had vowed to stop Ajimu from throwing her life away.