The reasons why no passenger aircraft larger than the A-380 exist (and why this one is having some difficulties) are overwhelmingly practical rather than theoretical. The basic story is that you not only have to make it big, but also light enough to carry the passengers, baggage and/or frieght that will pay the hideous purchase price, along with enough fuel to get where you’re going.
This isn’t any sort of issue in current designs. It’s safe to say that wings could be much bigger without falling off. It is fair to say sufficiently strong wings and main spars are both more expensive and heavier than they would be in an ideal world.
No inherent limits there. Really large aircraft can have good L/D - both the A-380 and the 747 certainly do (indeed, they must, in order that their fuel consumption be acceptable).
There are, but they aren’t principally realted to fuel economy (which is really quite good for giant aircraft, and indeed is one of the reasons for their existence).
Probably the biggest is simply the staggering cost (and risk) of developing a new design like this. Boeing is said to have “bet the company” on the success of the 747 (they won that bet, big time) and Airbus (EADS) is probably in much the same case with the A-380.
There are some sound real-world reasons why giant aircraft are challenging. The nature of our atmosphere makes something like 35,000 to 39,000’ the right altitude to fly at - you are above most weather and where air density and temperature makes modern jet engines happy. Giant aircraft would like to cruise a bit lower than that, and so need somewhat oversized (thus heavier and more expensive) wings to fly where they must. This makes it challenging to have your giant plane light enough to carry sufficient payload.
There are plenty of other issues. Not least is getting, say, 700 people aboard in a reasonable time (time is money - an A-380 will probably cost over $4000/hour just sitting on the ground). Baggage handling could get interesting. Runways must be strong enough to take the weight.
Another consideration is wake turbulence. When a large plane takes off it creates wingtip vortices that make it unsafe for another plane to follow for a certain time. Recent tests indicate what was expected - that the A-380’s wingtip vortices will be substantially worse than for any other aircraft. It may be necessary to double the amount of time before any aircraft is allowed to take off after an A-380. In response to this, airports have said that they will look at doubling the landing fees - it might cost an extra $30k or so. This would have a nasty impact on the profitability of an A-380, and thus could seriously hurt sales.