You may notice the regulars may seem disinclined to respond, just since the question gets asked so often. In fairness, though, the search function on Chowhound is really unwieldy. Why, for instance, you can't do a search and then sort by most recently posted is absolutely beyond me.
In any event, here's a good thread to start with though it's a little bit dated:
My tops in South Beach list looks like this:
Talula (mediterranean-influenced, varied menu, husband/wife chef team, a little more laid-back than much of SoBe
Mark's South Beach ("new American" or whatever you want to call it, good use of local ingredients, also a relatively quiet place by SoBe standards
Joe's Stone Crab (old-school establishment, though I don't know if it's still season
One more small notch down:
Johnny V @ the Astor Hotel (nuevo latino/caribbean; also fairly new; he had a restaurant here several years ago which I liked better, though I've only been to the new one once and it was shortly after they opened)
http://www.johnnyvlasolas.com (link is to his Ft. Lauderdale restaurant
)China Grill (a Jeffrey Chodorow "chain" with a few locations in the US; newfangled asian influence, served in family style portions)
Nemo ("new American" w/ something of a seafood focus; local celeb chef Michael Schwartz is long gone but it still carries on, though not as inspired as several years ago
Yuca (nuevo Cuban, also an "old-line" restaurant by SoBe standards but I've never had a bad meal; the guava BBQ ribs are excellent
I have never been to Prime 112 but have heard very good things. David Bouley has a new restaurant called Evolution in the Ritz Carlton, has gotten mixed reviews.
Here are some of my favs on South Beach, service and food quality can vary wildly from restaurant to restaurant but these are the ones I have found most consistent:
Talula- Excellent preperation and service, top knotch quality ingredients and the Risotto is always terrific
OLA- Nuevo Latino cooking at its best, always flavorful and exciting
Nobu- Sort of a high end chain but excellent Japanese (although very expensive)
Nemo- South Beach standby with great food and atmosphere
Prime 112- very scene oriented with large crowds and very tasty food
Sardinia- Very good quality regional Italian cooking, good wine list
Table 8- hot new restaurant, high quality cooking
Pacific Time- Lincoln road restaurant with good seafood
The Forge- Not technically SoBe but a legendary spot with spectacular decor and an unforgettable social scene
Havent tried David Bouley Evolution but have heard good things.