This line tends to be said in a sort of philosophical manner, like zen, like “when I find myself in times of trouble – let it be,” sort of thing. But I wonder if it might be a little less static if before this line Horatio makes a move as if he’s going to go stop this nonsense, given how fatalistically Hamlet is talking. In that case, “Let be” is one final plea to keep Horatio from interfering, rather than a monkish philosopher king intoning wisdom with his legs crossed and his fingers in a yoga pose.