For breakfast, lunch, or coffee, the classic is Confitería las Delicias (San Martín 2898, tel. 0342/453-2126), alongside Hostal Santa Fe; the juices deserve special mention.
Cafetería La Citi (La Rioja [1] 2609, tel. 0342/455-4764) is another good option.
The Círculo Italiano (Hipólito Yrigoyen 2457, tel. 0342/452-0628) specializes in pastas.
Triferto (San Martín 3301, tel. 0342/453-7070) features a diverse pizza menu.
Across from its namesake hotel, España (San Martín 2644, tel. 0342/400-8834) serves an outstanding garlic surubí (Paraná catfish), plus an exceptional arroz con leche (rice pudding) for dessert.
The Centro Español (San Martín 2219, tel. 0342/456-9968) is more elaborate but not that much better.
For fresh fish, the riverfront
El Quincho de Chiquito (Brown and Obispo Vieytes, tel. 0342/460-2608) is a Santa Fe [2] institution. Beneath a cavernous thatched roof, waiters serve large portions of grilled specialties like boga, sábalo, and surubí for about US$7–8; take bus No. 16 from Avenida Gálvez in the northern downtown area.
Via Verona (San Martín 2585, tel. 0342/455-4575) is the place for ice cream (a virtual staple in the steamy summer).
Links:
[1] http://www.moon.com/destinations/argentina/cuyo/la-rioja-province/la-rioja
[2] http://www.moon.com/destinations/argentina/mesopotamia/santa-fe-province/santa-fe