I like to maximize my time, so if I have weekends off, I fly down late Friday or early Saturday, and fly back home the following week late Sunday, and that essentially gives me two extra days that I wouldn't have (an extra weekend) had if I flew down and back during the week.
If you can't stay afford to stay down there the extra two days, then it gives you maybe a day before the trip, to get ready, and a day after to relax before going back to work.