If the modern airliner (Boeing/Airbus) was redesigned from scratch today without any need for "backward compatibility", would it look functionally different from the current design? And if so, what would be different?
You'll only get opinions here, but from 40 years in the business, my opinion is not much. Airplanes are a balance of compromises and after much trial and error, dead ends, and false starts, a combination hits a sweet spot in the balancing act and that becomes a near universal configuration. When someone deviates, it MAY create a new configuration paradigm, but most of the time the reasons the universal configuration works so well are revealed, or rediscovered, by deficiencies in the attempt to strike out on a new path.
And here we are, still building airplanes along the lines of the granddaddy of them all for this particular configuration, the B-47, 73 years later. Virtually all of the improvements that have followed are related to engines, materials and electronics.
Interestingly, you have a kind of mirror image of the same thing in the bizjet world. There, the tail mounted twin with fuselage hugging the ground is the design config sweet spot.