See no reason why the 747-8 can't have 2 engines turn off for cruise and descent.
The full power of 4 engines is only really needed for climb, emergencies, and to be available for go-rounds.
A couple of engines buried in the wing root with doors
that close for drag reduction could do the trick.

A 747-8 with the fuel economy of a 777 would be welcome.
Think about it.

Bob