I've purchased quite a few open box items from Newegg (including an Asus P5WS64 motherboard, and several video boards) and have never had problems with any of the items I've received, they've all been fully functional. Open box items have a 30-day return policy and I believe that they will refund your money without the normal 15% restocking fee so I think all you will lose are the shipping charges in both directions. A lot of time people return hardware that they think is not working when it could be working fine but the problem was either a configuration issue or an incompatability issue with some other hardware or software that the user had.
I must warn you that you may just get the motherboard by itself wrapped in bubble wrap with no manuals and/or accessories. So you may have to obtain an IO shield on eBay, and get the SW drivers and manual from the Asus website. In my case all the open box video boards I've gotten have come just wrapped in bubble wrap with no accessories, but I guess I lucked out and got the motherboard with all the goodies the retail models come with.