After visiting Santa Fe I would say that the Mesilla Plaza is smaller. The shops surrounding it aren't anywhere near as upscale as those in Santa Fe, though Santa Fe does have souvenir gift shops near its Plaza, too. Missing are Santa Fe's art galleries as well as its historic museums such as the Governor's Palace, which is right on the Plaza. Mesilla has no La Fonda Hotel on the plaza either the way Santa Fe does. Santa Fe also has more grass and trees, being at 7000 feet whereas Mesilla is between 3,000 and 4000 feet and doesn't boast as much greenery.
What does Mesilla Plaza have? There is a Mexican Restaurant, La Posta, right on the Plaza. But it's rarely open for lunch when we want to eat. There's a cathedral and a scattering of souvenir shops which aren't open all the time. In the center of the plaza is a gazebo. When they're not having a festival you can usually park right in front of the cathedral and walk around. It's a good place to walk your dog. An interstate stop --- yes. A vacation destination --- no.