9. The Lizard Eats His Son
Zeb Wells and Chris Bachalo's "Shed" storyline ran from Amazing Spider-Man #630 to issue #631, and it's actually pretty great. Taking a deep dive into the mind of Dr. Curt Connors and what it means for him to share that with the Lizard, the mild-mannered scientist is eventually overwhelmed by his other side, and murders his son in the process.
The line was blurred here between Curt and the Lizard in a big way, and while the story itself was effective enough, there were better ways to handle this than having him kill his young son.
The Lizard quite literally eats poor little Billy, and had this led to big things for the villain, it might have been easier to justify. Instead, Curt would eventually regain his mind, reunite with a cloned, Lizard version of his son, and then go on to return to his old status quo in Nick Spencer's current run.
Making a hard-hitting creative decision like this should change everything. Instead, it was just another throwaway tale in the "Brand New Day" era which is only remembered for the shock factor.