I am not an expert mechanic by any stretch, but I always thought that it was a matter of geometry. The distance that the fuel needs to travel through the manifold on a single carb is higher on the outer cylinders. When a fluid (liquid/vapor, etc) travels through a body (manifold), it is going to experience drag on the inner surface of the body and loss of velocity. By going to a multiple carb setup, the geomtery of the manifold is different, and allows for more efficient and balanced flow of the fuel to the valve. I suppose the trade-off is in the tuning and configuration. With multiple carbs, you must tune them together. Any discrepencies in tuning (mixture, etc) will be compounded. With regards to aircraft, I think you are on the right track. Mixture is much more important, given the changes in density of the air that is taken into the carb, and it is critical that your engine cylinders are performing in synch. Having multiple carbs, howver, means multiple points of failure. That, I think, is why you can adject mixture to each valve. At least, this is how I understand it. I have been flying on and off for a couple years, and have helped on the annual inspections a couple times, during which you normally get a whole ration of tech talk from the A/P mechanic.
I am by no means an expert, but at altitude, a tuned engine is peace of mind. On the ground, you can just pull over.