I would agree with most of what was already said, but add a few things.
1. Bring whatever cash you can afford (or feel comfortable having on you).
2. Plan your trip. i.e., Google your planned route ahead of time so you have some idea where the banks are, how many in each town, etc. If you have a cell phone with GPS/mapping capabilities you may not need to write any of this info down as it is likely available to you as you go....unless of course your route will be taking you into areas where you have no cell coverage. If that's the case, it may make sense to generate a bank list w/addresses and phone numbers.
3. If your bank roll can afford it, don't search at all until you get home. Time spent searching is time lost. That being said, if you are almost out of cash and have a location to dump, then by all means search and dump. Note: Searching while driving can be done, but don't attempt it in heavy traffic and if you do attempt it... be safe about it.
4. If you search denominations other than halves and you have a sufficient bank roll, ask along the way. You've already driven that far and potentially waited in line to get to the teller window. Of course, getting other denominations may require additional time at that bank and minimize your total number of stops....
5. Bring a container to put your finds in.
6. Plan your road trip on a day that banks have longer hours but won't be as busy to minimize time waiting in line to get to a teller. Generally, Fridays are busy as are times around the end of one month and beginning of the next.
7. The more heavily travelled a route is, the more likely that route has also been used more frequently by other CRH'ers (i.e., more competition). That being said, travelling to all tiny "out of the way" towns isn't a guarantee of success either. The only way you'll know is to get out there.
8. Realize that bank/branch policies vary and not all banks (and sometimes it seems teller dependent) will be willing to work with you to give you what you want (sometimes even if you have an account). In other words, be prepared to be turned away. In those instances, stay polite, accept it, and move on.