Outside the Colonial Zone, Puerto Bonito (Italian/Mediterranean) on Ave. 27 de Febrero near the intersection with Churchill is quite elegant and not so expensive. The food is delicious. Over US$100 for a lavish meal for two.
In the Zone - Museo del Jam?n (Spanish) on Plaza Espa?a is a good bet. Not as expensive as Puerto Bonito.
But if I had to recommend just one, Mes?n de Bari (mentioned above) on Calle Hostos in the Colonial Zone, with its typical Dominican cuisine and great atmosphere, has no rival.
There are others - any particular type of food? I was thinking Briciola (Italian, said to be the best in town) or Porterhouse (steaks) or the trendy fusion places in Naco...