I grew up in myrtle and live here now.
Seafood; Fried:
In town: Sea Captain's House or Chesepeake house in myrtle, Billy the Kid's or Horry's in North Myrtle.
Out of Town: Murrells Inlet, SC or Calabash, NC.
Murrells Inlet is worth it for the Marsh Walk.
Seafood; not fried:
Myrtle/north Myrtle- Collector's Cafe, New York Prime(Steaks as well), Ciao (Italian), Rossi's (Italian) Indo, (Thai/Sushi) Greg Norman's, Sea Blue (fucking awesome), 21 Main, Joe's Bar & Grille
South I'm not too sure about who has the best fresh fish in Murrells Inlet. For some reason I've never been blown away, but I don't go enough to be considered an authority. The Rice paddy in Georgetown, or Frank's/Frank's Out-back in Litchfield are really really good.
Plenty of good places to eat, most don't advertise on the beach channel. Unfortunately, most restaurant owners here seem to be happy catering to the stereotypical tourist that judges the quality of the meal by the obnoxiousness of the sign out front.
Oh- margaritaville is pretty good. I go once every couple years, in the winter. The wait is typically 2 hours minimum in Summer...