One of the most common arguments against infill systems is the concern over air leakage at gaps/beam interfaces and thermal transmission through framing members. Not much you can do about the main frame unless you are willing to install a layer of foam sheet on the outside (or
hide the timber frame). As for the other issues, consider an uncoupled wall structure (such as used in sound abatement). You end up building 2 2x4 stud walls, one for the outside and one for the inside. Provided you leave at least an inch gap between the two your foam should fill the void and break the thermal conductivity. A nagging thought says your savings would be minimal so I would question the economics but that is perhaps better left to someone who had the time to do the research. The other thought re: the infill/timber interface is to borrow an idea that I saw up at Canterbury Shaker village. Install a small spline in the post/frame so that you maintain an air block as the frame shrinks or things shift. What I saw at the Shaker village was that they rabbetted thier siding boards and used small splines to fill the gaps. Very practical as you did not have to worry about edging a board or damaging the tongue and pretty effective at restricting air movement.
Andy