My vote goes to Super Smash Bros.
This series of fighting games is unique and original. Aside from the premise of taking popular franchise characters and making them fight is the winning conditions. Depleting your opponents health bar isn't the goal. You build up your opponents damage until you can knock them off the stage and stop them from getting back. This concept mixed with rolls, spot dodges, differing character weights and fall speeds, four player battles and easy controls creates a game that is easy to pick up yet still very deep and difficult to master. Combos are completely dependent on situation and one string of the same button presses cannot guarantee a combo or a victory.
I also play Soul Calibur, Dead or Alive, and Guilty Gear series. However the greatest single fighting game ever created would have to be...
Eternal Champions: Challenge from the dark side
Look it up if you don't know.