If it's Aeronaut over Sky Train, decide if 3 -vs- 2 compartments work better (SkyTrain has 2 large compartments + a very small one on the front, so it's really only 2). I have the SkyTrain and prefer to have 2 larger compartments because I tend to use packing cubes, so smaller end pockets are not important for me. The Aeronaut has end pockets that some folks like, but I don't need them.

Moreover, if SkyTrain is my only bag, it's insanely simple to pull out a cube with my onboard stuff from the overhead since the 2 main compartment zippers are on 3 sides, including the top. If for example I'm in a bulkhead domestic, I don't have pull the entire bag out to access or stow the that cube for T/O or Landing.