Will pretty much force small and mid-sized online merchants to use a service that tabulates that tax due as orders are taken based on the shipping address, and then makes all of the payments on your behalf. Maybe they'll even do it for "free" by keeping the interest that accrues between collection and the monthly/quarterly payments, though that's probably too much to ask for. Costly up front if you're not using an off-the-shelf store front and have to pay your web developer to integrate the new tax collection/payment services. And then you'd need a method for including phone and mail orders as well.

I have to think many of the states will coordinate to standardize things and give a decent phase-in period to make life bearable for merchants. There will be plenty of chamber of commerce lobbying on this issue for sure. But someone will no doubt go off on their own and make things difficult for everyone (I'm looking at you, California). Yeah federalism!