I used to get 26/27 mpg for my 15 miles morning commute with front tire cold pressures of 38/39, rear tires were also 38/39. The problem was I felt front tires out of balanced a little, slight jumping up and down. Then I checked the recommended pressures posted on the driver door side of 32 front and 38 rear cold pressures. So I lowered the front tire pressures to 32/32. Guess what, now I am getting 24 mpg and front tires felt smooth. The acceleration felt heavier. My pressure gauge was pretty accurate compare to the air pressure pump at gas station.

I know the recommended tire pressures were the same for my previous 2007 GL450 with an 18 inch wheel. I think these labels were generic didn't take into consideration of the type of tires and engine. So, what is the best tire pressures for my 275/50R20 all-season run-flat tires on GL350?

I don't think there is an optimal tire pressure. It's always a tradeoff.

Lower tire pressure: smoother ride, better traction, but sluggish from a stop and reduced mpgs.

Higher tire pressure: harsher ride, less traction, feels more nimble from a stop, higher mpgs, helps better protect rim from potholes.

Wow. I may be too aggressive on the pressure: 38F/42R cold. It's no wonder I am getting 28 mpg on the freeway.

What wears down the tires more. More or less tire pressure?

If running low tire pressure, the edges of the tire contact patch will go bold first. If running high pressure the middle of the tire contact patch wears down first. Hard to tell which of the two wears down the tire faster without actual values of air pressure. Are we talking a couple psi here or 10+.

I would think low tire pressure wears down tires faster because there is more pressure from the two tire walls so two pressure points vs one in the middle

Any updates on recommended tire pressure for 2015 GL350 w/ 275/50R20 tires? I also noticed a major difference in the driver side door pressure guidance (39/47) versus the fuel door sticker (32/32). Right now I'm at 35/42 and I'm playing the middle range. Any recommendations as to what works best?

aggst1 has it right for the most part, higher pressure typically causes the center to wear faster and lower pressure the edges. But there's more to it than that. Optimum tire pressure is a result of weight and contact patch. You need the right pressure to create the proper contact patch and support the vehicle. Additionally, manufacturers like to run lower front pressures to create a bit of understeer to keep the handling safe, which is certainly less of a concern on big, heavy, SUV. There shouldn't be any issues running square pressures of 38/38 and certainly if you are towing a trailer I recommend pumping them up a bit more in the rear. Watch the tire pressures on the computer to ensure they don't creep over the maximum pressure on the sidewall of the tire itself and you'll be fine. I don't recommend pushing them too much higher than 40 cold, however as you'll stiffen the sidewalls and start to see poor handling over bumpy pavement, especially with run flats.