After you've run Audyssey's calibration with a subwoofer, you can change the front speakers back and forth between Small and Large without invalidating the calibration. However, you will loose the Low Frequency Effects channel, which is always sent to the subwoofer channel if the receiver has detected one.
Turn off the power on the subwoofer itself so that the receiver doesn't know it's missing. If you disable it in the receiver it'll insist that you rerun Audyssey.
Selden, this last part is incorrect. Audyssey only forces a re-run if you ADD speakers. Disabling the subwoofer in the receiver's Speaker Config will automatically change the front speakers to LARGE and reroute all bass (including LFE) to the FR/FL mains.