Which California city was originally founded during the Spanish mission era?

San Diego is the correct answer as it was the first city established in California during the Spanish mission era. The mission, Mission San Diego de Alcalá, was founded in 1769 by Spanish explorers and is recognized as the first of the California missions. This marked the beginnings of European settlement in what is now California, as the mission system played a significant role in the region's colonization and development.

The other cities listed have significant histories but were not founded during this initial Spanish mission period. San Francisco was established later, primarily during the Gold Rush era of the mid-19th century. Los Angeles was founded in 1781 but came after the establishment of San Diego. Santa Barbara, while also home to a mission built in the late 18th century, was founded as a community in 1782, after San Diego's establishment. Thus, San Diego's role as the earliest settlement during the Spanish mission period makes it the correct choice.