I kinda just let this sit for a few months since I had other things to work on, but I stumbled onto the solution today.
I changed the clipping at random and suddenly the big collider widget started blocking correctly. For reasons unknown, the UIPanel on my message box had a serialized mClipping value of 2, and I see that you've since taken 2 out of the UIDrawCall.Clipping enum.
This project has been through a few NGUI upgrades, so I imagine this isn't a common problem, but if other people have encountered a similar bug, check your UIPanel's clipping setting.
[EDIT] To clarify, explicitly re-setting the clipping to None (0) in the panel made it all work.
[EDIT2] I notice that I have to make the alpha of this mega-sprite at least 1 though, it can't be zero. Is there something I can do to make the UICamera not discard 0-alpha sprites for hit testing?
This is NGUI 3.7.6, Unity 4.5.