Clarksdale is considered the center of where the blues was born. Morgan Freeman’s bar there is called “Ground Zero”.
Personally, I liked it better before it became a blues version of Nashville, with all the tourist traps and higher prices. I admit that I’m biased because I used to play in bars there, but now the only acts they want (other than big names) are “local” acts, half of whom seem to have moved there recently from places like Long Island and L.A. But Clarksdale’s still got good live music, and there are lots of blues history sites nearby. If you love the blues, it’s worth multiple visits.
I’ve never been to Holly Springs.