I'm looking at this from both perspectives; as a consumer and as a small retailer.
As a consumer, it is not a big deal. I don't go to the internet for the purpose of skirting sales tax. Yes, it is nice not paying it on larger purchases, but I use internet sales mainly when there is something I can't go pick up immediately at a local store.
However, as a small retailer, the paperwork would kill me unless they also included some simple manner for recording and submitting to a single entity. Even in the metropolitan area that I live, there are several different tax rates depending on which suburb the sale is made. There is a single state-wide tax, but some cities also impose a local tax as well.
So even ignoring any local (city) taxes, it would still mean keeping track of 50 different state taxes, and filing 50 different tax submissions. The money isn't an issue because that just gets passed on to the buyer. It would be the bookkeeping nightmare it would "possibly" create.
For the large retailers, the added paperwork would not be a hardship, and many of them already have to do this for a lot of different states because they have a physical presence in them. It's the small retailers (like myself) that would get crushed by this. I have heard that some companies are advocating some sort of minimum threshold of either sales volume or company size before this would kick in. Then it wouldn't be so bad.