i have never tried a second stopover, but have upgrade itins with one stopover a number of times (sfo-hkg-sin; iad-sfo-pvg; sfo-nrt-pek) a number of times. this is one, and perhaps the only, area in which mileage-based U/Gs are superior to SWUs.

edited to add: once i even managed to get sfo-hkg-sin-hkg all upped with a single award (technically, sin was my destination, but they still let me do it.)