Well, from my point of view, all the discussion can be concentrated into a few points:
-1) Type rating commonality with 747-1/2/3/400:
Let's face it: The pilots who will pilot this aircraft will come from classic 747's; or the airlines ordering the new aircraft will replace/keep classic 747's as well, so they will love the flexibility they will have with their crew force.
-2) Maintenance commonality:
As stated before, a big advantatge in training, spare-parts investment, etc. If Boeing goes with the -5x/6x they will clearly adopt as many common systems as possible to keep the new versions as closely related to classic 747's as possible. That's one of the strongest selling points Airbus has used to sell so many aircrafts.
-3) Cheaper design cicle and, thus, adquisition costs:
I think every one will agree on this one
-4) Faster design cycle/entry into service:
What can I say? Obvious!.
The need for huge airliners might be tremendous in five years if ATC/airport congestion and traffic growth continue.
Let's remember than we are having a very hard, hard time in Europe right now!. So, although companies prefer frequent flights over crowded and concentrated flights, they might be forced to stick to the latter option in the next ten years if air congestion grows.
Hence, the manufacturer that gets the giant airliner to market earlier might get the big orders.
5-- Older technology:
Meaning sub-optimum performace compared to the A3xx or NLA, but basically on fuel burn performance only!
The question is wether the first 4 points compensate for the higher fuel compsumption of 747-the 5x/6x. Let's remember that operation costs are related to fuel effiency only on a percentatge. Then, there is financing, maintenance, crew training and other costs that might overrun fuel effiency advantatges.
So..., what's your opinion? Mine is that it makes a lot more sense to build the 747-5x/6x than a completelly new design. Fuel effiency, from my point of view, is not enough to go with a completely new design.