So far I have been looking only the aerodynamics side, but it is quite evident that compromises are needed on the aerodynamics side to achieve the best structural efficiency. I think one good example is Virgin Global Flyer (Scaled Composites model 311). I have not analysed yet the structure, but common sense says that trimaran has weight placed more evenly along the wing span avoiding a very large point load in the middle where the single fuselage would normally exist. The trimaran may have more wetted area than a single fuselage, but on the other hand, weight savings in the very high aspect ratio wing and space gains for the extra fuel are in this concept very important factors.
I find the trimaran configuration quite interesting - several different engine placement configurations for example can be used with this configuration without changing the aerodynamic shape of the concept very much. It is also interesting because it allows placement of the main gear away from the center fuselage and thus provides greater stability on the ground when the aspect ratio is high even if there is fuel placed to the wings very far away from the center of gravity. And as can be seen the same design suits several different missions: Global Flyer is very much like White Knight 2 with SpaceShipTwo under it on the center. Almost the same configuration, adapted to different kind of mission for very different kind of parameters (Global Flyer = long range cruise, White Knight 2 = optimized for climb).
Global flyer drawing Google found from some site
Wikipedia has another great photo, this is from front
The configuration is not really so new and not so unproven either, as people might expect, here is one example where a similar configuration has been used a long time ago:
The only difference here is that the Northrop Widow was optimized for different mission than either of the abovementioned and that it had piston engines in front of the outer "fuselages" which were interconnected from the tail section similarly than in Adam A500 whereas the Global Flyer and White Knight Two have two separate tails. It is quite apparent why the tails are separate in these aircraft - because the outer fuselages are placed so widely apart from each other, connecting the tails would have made the tail unnecessarily large which would have caused negative effect for the drag despite it would have had fewer intersections. On the other hand, I have been looking different HALE concepts, and it is quite apparent that the number of intersections is not the major drag source in high altitude aircraft, but the induced drag is, and to minimize induced drag, more intersections can be allowed as the penalty from them is lesser than limiting the aspect ratio would be. This is why there are even some concepts considered at the moment which have wing struts - even if everybody knows that they produce drag, in some concepts, the significance of that drag can be proportionally small whereas the increased aspect ratio has major effect on minimizing the total drag of the aircraft. HALE aircraft have to be quite different than those which are designed to cruise at low altitude, the drag percentages of each contributors are quite different and "one size does not fit all".
It is quite interesting area to explore when the structural efficiency is added to the equation in addition to the aerodynamics and the result is a compromise on both structures and aerodynamics instead of being optimized for either aerodynamics or for structures. The mission parameters tend to heavily affect both and best suited results can be achieved by combining these two and by knowing the intended use exactly, potentially bigger gains can be realized than in a concept that is a general purpose in everything (GA = GENERAL aviation).