República is the historic section of Sao Paulo's downtown, forgotten for a while by the cool kids in the late 20th century, but hitting a resurgence in the last decade or so with its unique variety of nightlife and a great selection of Italian and Brazilian restaurants.
What makes the nightlife sensational here is not the vast number of clubs or bars or other hot spots, but the intriguing range of what is represented. The Lions Club and Hot Hot are exclusive clubbing at its best, Bar Brahma hosts some of the best Samba around, and an establishment like Trash 80's describes itself quite fully by name. Take a walk along Rua da Consolação if you're looking to find a high concentration of nightlife.
As far as cuisine goes, Rua Martins Fontes and Avenida Ipiranga both overflow with options near where they connect to Avenida São Luís, which also has your bases covered. Estadão Bar & Lanches has your sandwich fix, Famiglia Mancini is some of the best Italian outside of Italy, and Brazilian specialties can be had at institutions like Bar da Dona Onça on Ipiranga.
Note:Republica is also home to the oldest gay section in the city, located on and around Largo do Arouche.