Both lakes are popular recreation spots. Lake Murray is very busy, particularly on weekends, due to its proximity to the Columbia area. I've never seen any data on the number of vacationers, but both have a number of campgrounds that stay busy. IMO, Murray is a prettier lake, but the crowds can be a turn-off. Largemouth bass are probably the most popular fishing in Murray. B.A.S.S. has staged several tournaments on the lake.
Santee Cooper (Lakes Marion and Moultrie) is relatively shallow, loaded with standing timber. It was being built when WWII broke out. Most of the engineering and construction crews were diverted, the dam was finished and then the lakes were flooded without the usual clear-cutting. Navigation requires paying attention, but the channels are generally well marked. Due to the shallow water and surrounding flat land, Marion can get rough during bad weather. In the 50's & 60's fishing was fantastic, primarily largemouth bass and striped bass. A little trivia - Santee Cooper was the first lake to have landlocked striped bass - occurring accidentally when the dam was built. Their popularity led to building a state-operated hatchery on the lake for striped bass. This hatchery introduced stripers to numerous lakes all over the country. Hydrilla became a problem a couple decades ago, and has really choked off portions of the lake. There's a large ongoing program to eradicate it, or at least control it. The most popular fishery now seems to be channel cats and blue cats. Earlier this year, a blue cat weighing over 130# was caught on a trotline in Moultrie.
Here's the latest
SCDNR Fishing Report.