Christine Gibson at American Heritage:
Crowds from across Spain lined the streets of Seville in 1493 to welcome him home from his first voyage to the Americas, but he already hadn’t found what he was looking for, a seaway to India’s spice-trade ports. He never would, though the search consumed the rest of his life. A little genocide here, some slavery there, several mutinies, and multiple executions of crew members later, and Columbus fell out of favor with the Spanish crown and the public. When he died he was surrounded by family and by the trappings of his substantial income. But he went to his grave with the gouging sense of injustice he couldn’t forgive and of failure he couldn’t explain.
His reputation began to sour during his second expedition.