I'm calling it a four-way tie out of the list there: Makoto Shishio (Rurouni Kenshin), Zatoichi the blind samurai (Zatoichi films), 80-year-old Bruce Wayne (Batman Beyond), and Teddy Roosevelt (Kickass President).
Shishio and Zatoichi win for being extremely-skilled samurai would beat the shit out of everyone despite having seriously-handicapping conditions. Shishio himself cannot fight for more than fifteen minutes thanks to being burned alive in a manner which prevents him from letting off most of his body heat. Anything more than fifteen minutes of heavy exertion will kill. Fortunately, he hasn't needed it. Zatoichi, of course, is blind. Everything he does cannot be done visually at all. He gets by through what he hears, smells, and can touch. So far as I know, nobody has touched HIM, so it must work out very well.
Bruce Wayne is, of course, the retired Batman, still as capable mentally as he always was. Though he's old and has a heart condition, no street thug is a match for him. He's still the brains of the operation and can kick a fair amount of ass. The only problem is whether or not he can stand the strain. As for Teddy, well...he was born an ill child, his body weak and his eyesight requiring glasses. AND YET, this is the man that kicked weakness on his ass as he worked to overcome his handicaps to land himself first into the military with some successful and violent charges, and then become President Badass. (My guess is that we could see a movie along the lines of Teddy Roosevelt: Werewolf Hunter, and it would WORK.)
Honorable mention to Bruce Lee, who - during his life, training, and career - sustained an injury that should have put him out of action permanently. Instead, he worked even harder and redoubled his efforts to become even stronger than before.
