To be sufficiently efficient, it really needs a 747-800 or 787 level redesign. That will not happen. Simple numbers...the empty 747-400 weighs about 185 tonnes, and carries around 370 people in a reasonable configuration. An empty A380 weighs in at 285 tonnes empty, and carries about an extra 100 people in a similar configuration. Basically its empty weight is far too high for it to ever become 'efficient'. Lose 50 tonnes and it would work...but that's really not something that can be done with the current design. There will be lots of tweaks, but that's all they are.
As much as I like it (the 380), the reality is that the 787 and 350 are the future. I even have my doubts about the 777X.