So all the main villains in the manga hate the Leaf for almost the same reason:

Madara hates the Leaf for not picking him to be Hokage and for the disrespect given to the Uchiha Clan

Orochimaru hates the Leaf for not picking him to be Hokage and for stopping him from experimenting on human subjects (temporarily)

Obito wanted to be Hokage but died loving Rin who may have loved Kikashi. He blaims kakashi (a Leaf ninja) for not protecting the only person he loved in the world so the world needs not to exist anymore.

Sasuke hates the Leaf for ordering the destruction of his clan by the hand of his brother,Itachi. Sasuke lost everything that he loved at the hands of the brother he loved most.

Danzo wanted to be Hokage but was overlooked by the 2nd for Sarutobi. he never gave up trying to become Hokage but used any method at his disposal.

The interesting part is the 6 degrees of separation with Orochimaru. I bet that Oro never really left Akatsuki. He left and kept the ring so that he couldn't be replaced. You telling me that a bunch of missing S class ninja allowed him to leave and never pursued him. He who knew their plans to destroy the ninja world.Thoughts.....