I believe there will always be the odd business who will bar the use of higher denominations due to contextual reasons. Some of these may be gas stations or fast food places where managers have a high turn-over in staff, or don't train the staff well enough, so they'll always ban the use of $50/$100 no matter how secure the currency. Most mom&pop shops will maintain a conservative policy of what type of denominations they will accept, and I expect that will remain the same for some time.
Other situations may also bear on whether a business takes a higher denomination: such as, a manager transaction vs a p/t staffer, the age and deport of the customer, etc. If a business (such as furniture, or used car sales, etc) is under the gun to meet a sales quota I doubt there would be as much hassle with a higher denomination (to pay for a high ticket priced item) vs a Mack's convenience store for slushy. As suggested in an earlier post, some major retailers (such as Costco which only accepts American Express credit) will have to deal with higher currency & will likely continue to do so for some time as a convenience to their client base.
As times change, I would expect most service/merchandise staffers expecting their clientele to use credit/debit transactions rather than higher polymer currency but I may be wrong (there are always exceptions). Now that credit cards have a chip (with PIN# verification) & have become the desired method of payment for high priced items, I still tend to believe that will be the preferred way of the future.