I pick John C Reilly purely because he is a good actor. The variety of roles he has played in his career, have earned him various awards and acclaim across Hollywood. Playing The Doctor would be a brilliant choice for him. He could pull off both the serious side and comedic side of the character, given his past roles and experience within various genres. I reckon he could strike a Doctor very similar to maybe Christopher Eccleston. Funny and warm hearted, but never afraid to let out his serious side. Reilly in many ways is a camelion actor, and really would be a perfect Doctor for many fans. So again, he can be either a light hearted, whimsical and adventurous Doctor. Or maybe, a dark calculating take on The Timelord, much like The First & Seventh Doctor combined.