I get 22 mpg at 75-77 mph with a family of four in the truck. If I keep it below 70 mph (like on U.S. highways vs interstate), I've averaged 23.5 mpg. These are averages over 250-300 miles, not instant mpg.
As far as MDS goes, I can definitely feel when it's on. The truck shudders slightly, especially if you "squeeze" the accelerator just a touch, but not enough to deactivate the MDS. (BTW, this was EXACTLY the same experience I had with my Honda Pilot's VCM, so it's apparently characteristic of cylinder deactivation systems.) It doesn't bother me on the highway, but I'm not a big fan of it around town. I will generally turn it off in the city so that I get immediate response to the slightest throttle inputs.