Don't listen to those who say you're taking too big a chance. [If he had], Michelangelo would have painted the Sistine floor.

Simon’s quip is a comic encouragement to ignore timid counsel when pursuing ambitious work. By invoking Michelangelo and the Sistine Chapel, he frames “taking a chance” as the necessary condition of artistic or personal achievement: great results often require accepting discomfort, risk, and the possibility of failure. The punchline—painting the Sistine “floor” instead of the ceiling—turns the idea into a memorable image of how fear can literally lower one’s sights. The line also reflects Simon’s broader sensibility about craft and courage: creative success depends less on playing safe than on committing fully to a daunting task.