Quick disclaimer/thanks: Most of the information below was shamelessly taken from Costa Mesa and Newport Beach city websites, the Costa Mesa Historical Society and Newport Beach Nautical Museum writings, books on local history and Wikipedia.
In rough chronological order, here are my initial picks:
Members of the Tongva and Juaneño/Luiseño nations: These Native Americans made Newport-Mesa their home for thousands of years before the arrival of Europeans in the 16th and 17th centuries. The hunters and gatherers staked out some of the area's prime real estate, including the riverbanks of the Santa Ana River and land above Crystal Cove.
Diego Sepulveda: As the Spanish land grants were partitioned in the mid-19th century, Sepulveda, the former municipal magistrate for the Pueblo de Los Angeles, around 1868 acquired property in what's now Costa Mesa. He expanded a small abode home — used to house herdsmen and missionaries from the San Juan Capistrano Mission, and located near the banks of the Santa Ana River — and made it his home. It was the first non-Native American home in the area and remains the second oldest existing building in Orange County (the chapel at the San Juan Mission is older).
Gabe Allen: Seafarer, trader and pioneer. Owner of a wild, bushy beard long enough to cover up his collar. In 1870, he bought 2,760 acres in the Costa Mesa area owned by Sepulveda for $10,500. He lived on the property for 16 years and subdivided the land to farmers, leading to the early short-lived communities of Fairview and Paularino.