As far as zeroing between bit changes, yes, I always use the same spot - the center. Yes, a lot of the center area has been cut away, but there is enough there that my touch pad can span the piece. I've also tried cutting on different areas of the table, and always get the same results.
Is the stock perfectly flat before I start? It's as flat as I can make it.
I've also tried running the virtual set-up between bit changes, just in case the clearance path causes the piece to bow a titch. And I've also used the same virtual settings between bit changes on the assumption that there is no bow as a result of the clearance.
I did have a problem with the coupler for the X-axis once - really threw me for a loop until I talked with the guys at Next Wave. But since then, I've checked all three axis again, and the couplers seem to be tight - I don't think there is any slippage there.
One thing to try would be to run a larger diameter bit over the blank, taking off just a hair to make sure that it's surface is parallel to the bed.
Oddly, I did a sign for a client a week or so ago that was just simple flat-bottom recess - not a text-on-text - but I used the same technique of running a 3/16" clearance tool path followed by a 1/16" detail tool path. They were even the same bits I'd been using previously, and there was no error in that.
I have not tried to zero my Z axis by manually. That seems very subjective and prone to even small errors as you suggest. But maybe I do need to try to zero off the piece somewhere that isn't touched by ether of the tool paths.