Over the past couple of days I’ve managed to drive for about 12 hours. And as anybody over the age of 40 knows, just sitting there not moving really allows the blood to pool in your legs and feet.
Various articles, such as this one from eHow suggest “wearing shoes which slip on and off and are easy to remove if you notice swelling.”
Of course, if you drive barefoot, you’re one step ahead of the game.
It also allows you to exercise your feet while you are driving. You can do all sorts of toe clenches or various toe and ankle wiggles that will help push that blood back up to your heart. I’ve found that that really helps me. Here’s a nice article by Myranya that talks about that in the context of flying barefoot.
I have another technique for when my legs start feeling heavy that really is easier to do when barefoot. I’ll sit cross-legged.
Let me stress that I only do this in low-traffic situations on Interstates. I set the cruise-control and then sit cross-legged. This is fairly easy to do when barefoot (but ridiculously hard if you are wearing big, clunky shoes—and all shoes are big and clunky compared to bare feet). If I need to, I can quickly slide my feet back down to the brake or gas pedals. If it concerns you having both feet up, you can do it with just one foot at a time, and drive with the other foot (and, yes, I practice driving left-footed, just for the heck of it).
Some of the articles say not to cross your legs (these are airplane articles, not driving articles), but I think that refers to crossing your legs with your feet still down near the floor. I’m talking about raising your feet to your seat and sitting cross-legged.
The point is to get your feet and legs closer to your heart.
I find that it works for me.
Ahcuah 
Great suggestion Bob. Although you have to watch that you don’t pinch the blood flow and make your legs go numb. I have that problem on occasion when I pull my legs up.
Good point, Tim. While cross-legged can help blood flow, it can also put pressure on nerves that leads to numbness. So one should be careful to make
sure that one still has feeling.
At an advanced driving course, the instructor told us about ways of detecting and fighting drowsiness. He said that taking off your shoes and driving barefoot was a very efficient way of staying awake because of all those nerve endings in feet being stimulated.
I don’t know however if it works for a barefooter. For a habitually shod person, the sensation of bare feet on pedals may be novel enough to keep him/her awake, but for us it’s something we are used to.