Which character in The Great Gatsby is most responsible for the death and destruction that takes place in the novel?
This question requires a subjective response as there is no way to directly prove that one character is more responsible than another for the three deaths that take place in the novel (Myrtle, Gatsby, and Wilson).
In my opinion, Jay Gatsby is most to blame for these deaths. In order for him to get what he wants (marriage to Daisy), he has to break up Daisy's marriage. Daisy's child should be a concern to him, but isn't. Also, his insistence that she tell Tom she never loved him puts Gatsby in the wrong and makes him a bully very much like Tom.
We can also argue that Tom's infidelity did not drive Daisy to her dalliance with Gatsby. Gatsby would have pursued Daisy's affections regardless of Tom's behavior in his marriage. This makes Gatsby, ultimately, more responsible for Daisy's mental and emotional state than Tom.
Though Daisy drives the car that kills Myrtle and Tom leads Wilson to Gatsby's house to kill him, it seems that none of this would have happened if Gatsby had at any point relented in his pursuit of Daisy.
Gatsby drives the action of the story and so, in my opinion, is responsible for the outcome.