I don't know about "best", but some of my personal favorites include:
Taranta, which covers a broad swatch of Southern Italy, including the big islands, does great seafood, and has a few dishes that feature some interesting Peruvian accents.
Vinny's at Night, more of a Sicilian-American kind of place, cheap and mostly delicious.
Daily Catch (North End location only), which specializes in Sicilian-style seafood, especially squid. It's no reservations and cash only.
La Campania and Da Vinci, two similar Campanian fine-dining places with good mostly-Italian wine lists.
Gran Gusto, which does the closest thing to real Neapolitan-style pizza I've found.
Other places that do mostly Neapolitan-inspired Italian-American cooking pretty well include Massimino's, Pagliuca's, and Rabia's.
I'm a fan of Carlo's Cucina Italiana in Allston, an Italian-American place I'd say has a more Southern focus.