Joe Shuster's iconic Action Comics #1 from 1938. This cover has been burned into culture and marked the beginning of the Golden Age of comics. I couldn't picture Superman without seeing this image or Christopher Reeve catching Margo Kidder.
As part of Orion Martin's project, X-Men of Color, he reimagined this famous X-Men cover by recoloring two characters as brown. This cover comes from a storyline in which mutants are being rounded up and exterminated by the government.