A 19" tire will give you a better ride, but will the GLE system automatically adjust itself to the different offset and whatever else might change from the different wheel size?
I should add that I am in the process of ordering a 2026 GLE450, am looking for the most comfortable ride, and will use the SUV mostly on the highway.

As you said, if you want the most comfortable drive, go with the 19" wheels. If you order it this way, everything will be set for it (including the speedometer).

Looking at the configurator, 19" wheels are not available on the GLE 450 - only the GLE 350. I recently test drove a GLE 450 with the 21" inch wheels and the ride was great. With 20" inch wheels you should be fine.

iMO 19s are too small visually this size car and the ride with 20s is just fine.

How would you reset the speedometer if going from 21" to 20"?

When going with a larger wheel you use lower aspect ratio tires to keep the OD about the same; e.g. Pirelli Scorpion Zero All Season 275/55-R19 = 30.9", 275/50-R20 = 30.9", 275/45-R21 = 30.8".

The current build page for the 2026 GLE 450 doesn't show a 19 inch wheel option anymore. If you want the best ride, order the 20 inch wheels with the air suspension. It appears that the AMG appearance package is now standard with the GLE450W4. The 20 inch wheels are also standard.

All I know is that the comfort level from my summer 22s to winter 20s is very noticeable. I'm a spirited driver but I also appreciate comfort. The 20s are definitely a very comfortable ride.

The original tires for 19" wheels were too small (narrower, less side height) and not a good choice in terms of road safety. I think a couple of years ago Mercedes changed the specs for the 19" tires with wider ones.

In any case, the best choice is to go for the 20" wheels. Just keep in mind that while the front and rear tire size are the same, the front and rear wheels have different offset and can't be rotated. If you want to rotate tires, you'll need to dismount them from the wheels and reinstall them.