Any harm setting them to large will be largely dependent on the amplifier, source material, volume (which is largely dependent on your seating positions and personal loudness preferences).
Having the speakers set to large with highly dynamic blu-ray soundtracks could cause stress or compression due to some low-frequency content at loud volumes being sent to the mains or possibly inducing amplifier clipping damaging the tweets. Mid to low frequencies is what could really cause the current demand to ramp up, particularly problematic with a run of the mill AVR (clipping, overheating). Having the speakers set to large will require more power than having them sent to small. Your EP500 with its own dedicated internal amplifier and woofer designed to handle content between 20hz to 80hz is better suited than the mains.
