The default route doesn't have too many huge cities. Assuming you still want to take highways for a faster drive instead of smaller roads, stick to I-40 for the initial part of the trip. You can stay on I-40 to go past the north end of Little Rock, or if for some reason you want to see something south of the city, you could use I-430 and I-440 to bypass the main center. Getting back on I-40, when you reach Memphis, you probably want to connect on I-55 to I-22. There is a bypass highway (I-269) that was recently completed, but it's more useful for a north/south route. Maybe try taking I-55 south to connect to I-269 east that gets you to I-22. From there, you're really not going to hit any major cities. You pass through Tupelo, then when you get to Birmingham (Alabama), you can connect to I-65 south. Birmingham has I-459 as a bypass, but again it goes the wrong direction so it's not that useful for your trip. You could try to do I-20 south to I-459 east to get back to I-65 if you really want to avoid as much as possible in the middle. Take I-65 through Montgomery, then cross over to smaller roads whenever it makes sense to get to Panama City Beach. Have a great trip!