When I am working on separate pieces requiring accurate positioning of with the CNC, I spot the holes with a countersink, drill and undersize hole, run a circular pocket routine to the diameter required for reaming and finish with the ream. The circular pocket routine eliminates any backlash considerations and the ream will follow the hole defined by the pocket.
I put a 3 x 4 grid of 3/16 reamed holes on my CNC mill table for mounting a sub plate. When I have work that exceeds the work envelope of the mill, I can shift the sub plate and appropriately redefine my coordinates and continue machining. I have not had any problem with mis-registration for these light press fits.