Hand Drawn animation method

I am new to game creation and game art, so I am looking for someone to lend a hand.
I am a big fan of hand drawn animations. For example if anyone has played castle crashers, Skullgirls, or the quite recent norse mythology game “Jotun”, then you should understand what I mean by 2d hand drawn games. See, I consider myself pretty decent at art and the game I have in mind is fairly simple, however, I still want to implement my art. I will be creating the game in 3d, however the view is orthographic, so my art will be flat. My main questions are should I be using adobe flash, photoshop, or animate? Should I make a sprite sheet or do I just create framed animations where I just draw over the last image on a new frame? I also checked Hand Drawn Video using flash but,I got little confused.How can I import my art? Should I have a separate document for each animation?