Actually, it's more than just engine related. There's usually a speed where the whole coach just feels right. I know it's a subjective thing, but after you've driven a rig at various speeds for a while, you'll know where that speed is. It's a combination of engine RPM and torque, drive train vibrations and how comfortable you are at the speed. And it may be more than one speed depending on road conditions and type of road. I like to run the Sahara at 64 on the highway. Some 2 lane roads in Texas have a 75 MPH speed limit, but I really don't like to run 64 on 2 lane roads unless I can see way in front of me.
On these roads, I keep an eye on the rear view. If it looks like I'm holding up traffic and there's a Bambi afraid to pass, I'll pull over.
Also, company 18 wheelers are governed, usually around 65. These guys are working, and I'm not, so I'll pull to the side, slow down and let them slide by.
If you go only by mileage, then it's all physics; the speed you get in the highest gear at the lowest RPM. However, you won't make any friends running 50 on a 75 mph road.