Yes; and Boeing does do that (the 747 that ships today is almost an entirely new plane from the one that shipped in 1969), but the limiting factor is the 4-engine design. We don't have engines available that would let you build a 2-engine 747, and as long as we don't, they're going to guzzle a lot more fuel than 2-engine designs.

That said, apparently Airbus doesn't agree that 4-engined planes are going extinct, because they just recently finished a brand-new jet, the A-380, which requires 4 engines to fly. Go figure. Time will tell if that was a wise move on their part. But I'm guessing: no.

The 747-8 got a new wing, making it 16% more fuel efficient.