I'd love to see a 5.5" or 6" blade folder from Spyderco.
Like many others have said if I need a utility knife that large, than I will get a fixed blade - but as a combative tool, I think a large folder has a lot of potential. You can carry a lot of blade in a smaller package than a fixed, this makes it easy to conceal and comfortable to carry day in and day out. The SpyderHole is arguably the fastest of any thumb-opener to access under stress, another advantage to a Spyderco made mega-folder. A lock system like the compression lock seems ideal to deal with the extra leverage that a large folder presents, and this could also make it possible to offer something similar to the RAD, with a sharpened false edge for those who would use the BackCut technique with a folder. Of all the locks out there I think I'd look to a compression lock to handle this sort of force before any other. So yes, I'd want it to be a fighter style - those who would carry such a large folder would seem to be those most interested in it for defense, just looking around the forums and looking at the guys I know who carry mega-folders.
The way I'd like to see it done is in a sort of clip point style, G-10 handles, dual liners, compression lock, S30V blade, with integral guards/horns (I know this is common with other popular mega-folders right now, but I think these have a purpose, for those who know how to use them as part of their defensive tool, and if nothing else for superior guard from other blades, and for hand security. Done right they could be like smaller Gunting ramps even).
Something like this, just to give you an idea of what I mean:
A second version of a Spyderco large folder could be done with a half-handle and kydex sheath, for a RAD type effect. The RAD isnt the first folder like that, as PhilL pointed out the late 1800's saw many folding bowies like this, so it would be cool to see Spyderco use the idea as well, even if in a limited run or something.
Just my thoughts.