Well, in 2016, shortly after the coil-over conversion, I drove the S600 from northern Virginia to St. Augustine, Florida. Mind you, this is with 19" AMG wheels and thus lower-profile tires, so less cushion in the tires. The trip is about 11.5 hours of driving, and about 750 miles each way. I chose this car for this trip specifically to test the comfort of the new coil-springs. When we got there, I was not really tired, and I had done all of the driving with one stop for a late lunch. The car drove very nicely and was remarkably comfortable. Due to my not knowing about the ABC pump's need to always have fluid in it, the pump failed while we were down there, which was a big problem. Had I done the right thing and routed the pump's ABC output back to its input like it is now, I would not have had a single problem on that trip, so that's really my fault, not the car's.
Now, for driving around town, well, St. Augustine is one of the few places in the United States with cobblestone roads, and those cobblestone roads aren't the smoothest in the world. We could feel the road, of course, but not objectionably so. I expected it to be worse.
The next year, I took another road trip in the S600, not quite as far, but about 500 miles total. Again, it felt fine. I myself remain a bit surprised by how comfortable the car is.
It's also important to understand that tire make, model, and size plays just as big a part in the comfort of the ride as the suspension does. Let's talk about that.
Remember, I'm doing this with low-profile tires on a set of 19" AMG wheels (these wheels came from a W215 AMG car, probably a CL65). The tire sizes are 245-40/19 in front and 265-35/19 in back. Tire model is Michelin Pilot Sport AS3+. S600's, like S55 AMG's, actually come stock with 18" wheels, and why 19's are on there is a long story having to do with the previous owner.
I also have an AIRmatic-equipped 2003 S430 with the AMG Sport Package, which means the stock 18" AMG wheels, with the exact same model of tire as the S600 (Michelin Pilot Sport AS3+). Both are comfortable, and the 18's even more so than the 19's. Tire size on all four corners is 245-45/18. Previously, this car had Bridgestone Potenza RE970 A/S tires. They work well, too, with plenty of grip. Two years ago, I took this car, with those Bridgestone tires, on a 1,600-mile road trip to Georgia and back and wasn't really tired after in excess of 12 hours of driving, either way. Those Bridgestone Potenzas are good, and I would use them again on a car. The Michelin Pilot Sports are even more comfortable, though at the price of a bit of snow/ice traction, where the Bridgestones did somewhat better.
Now, I do have the front anti-sway bar and AIRmatic lower control arms installed on the S600, for better handling. You don't really need it, but you'll want it. So equipped, the S600 is quite fun to drive; I have no problems taking corners at speed. But what about the rear anti-sway bar? Well, the rear one isn't needed at all, because the car handles rather nicely with just the front one, while retaining ride comfort. That said, since I'm a masochist and a tinkerer, I'm going to try it probably next year, just as a fun experiment (requires lowering the rear subframe to do it).
Dave2302 · updated 
