Mouse and keyboard aside.
I was discussing this with an acquaintance today, and was wondering what other people thought. I really love the n64 controller (which also gets bonus points for popularizing the analog stick) but they thought it was the "worst controller ever made." Another person jumped in and also said that the n64 controller was unwieldy in their opinion. I just don't understand that. I've been using it since I was 5 pretty regularly, and have never had problems with little hands or adult-sized hands.
My runner up is the 3-button Genesis controller.