Having lived in California 60 years, and having done enough Calif. road trips to visit every county at least twice, and some dozens of times, I have visited all but one mission, San Rafael just north of San Francisco. You can't really say one is "better" than another without saying what it is you find better. Some missions are merely a footprint of the original (e.g. Soledad), some have become state parks (La Purissima and Sonoma), some are still (or again) operating Catholic churches, and some are merely historical sites. As CWsocial says, the replicas at the Cline Winery in Sonoma county are very interesting and well-done. And the winery is lovely, with good wines, lovely picnic spots, and reasonable prices. We almost always stop there if we are in Sonoma valley wine-tasting.
Mission San Juan Capistrano, Mission Santa Barbara and Mission Dolores in San Francisco have artistic and architectural beauty. Mission San Antonio de Padua and Mission San Miguel Arcangel are notable for their original frescoes and preserved churches, and for the devotion of their parishioners. Las Purissima (near Lompoc) is operated by Calif. State Parks agriculturally as in mission days, so it does great in recreating mission life. So does San Juan Capistrano. Visiting all 21 missions is my goal, so one day I will get to San Rafael. By the way Junipero Serra's tomb is in the mission in Carmel.
Whatever your feelings about the Franciscan friars or the Spanish government in early California, the mission system is part of Calif. history. As others have said, I wouldn't do a trip to see all the missions at once. Visit the San Diego area and see three missions on that trip: San Diego de Alcala, San Luis Rey, and San Juan Capistrano. From Los Angeles you can visit San Gabriel and San Fernando missions in L.A. and San Buenaventura in Ventura. On a central California/Santa Barbara trip, visit Santa Barbara mission, La Purissima Concepcion, San Luis Obispo and Santa Inez. Next up Hwy 101 is San Juan Bautista, San Miguel Arcangel, San Antonio de Padua and Soledad. Not too far apart near Silicon Valley are San Carlos Borromeo (Carmel), Santa Clara de Asis, San Jose and Santa Cruz. From the San Francisco area you have San Rafael, San Francisco de Asis (Mission Dolores) and San Francisco Solano (Sonoma).
So you see, many road trips are needed here to cover all the missions, but they are as good an excuse as any to have at least one.( I LOVE Calif. road trips!) But along the way to and between the missions, there are lots of other things to see and do. My hubby and I often follow the odd road and find fascinating things here in the Golden State.
We have mountains, desert, ocean and golden rolling hills dotted with California Live Oak trees. Also, active volcanoes and surprisingly, a handful of covered bridges!
Oh yes, if you have heard of Huell Howser (RIP), he did a fantastic tv series on the missions. See if you can find it and it will inspire you. Hope you can get to California and relish its variety. (And yes, Hwy 1 north of San Francisco is a beautiful road trip. I can't begin to tell you of all the wonders you can see on Hwy. 1 in Calif. and Oregon!
Come visit us when you can!