Assuming the concentrating of visitors is consistent with your business goals (and it sounds like it is), you should run a national campaign behind the regional as a backup, at a slightly lower bid. (Conversely, if you want nobody from outside your target areas, I'd say skip the backup plan cuz it's to hard to avoid everyone else in the nation.)
The amount you should lower your backup national bids depends on your how strong the geographic exclusion factor is (how bad the untargeted areas are for you regarding conversions). You need the backup national plan to cover lots of traffic that won't be properly identified by IP and the other factors G weighs (to determine location).
It can help to include negative keywords in your backup plan to avoid the areas you want to avoid. Nobody from Alabama ever buys, add Alabama and it's major cities to your national backup negs.
Let's assume Boston is an area you want to target. G will point two types of searchers to your "Boston" focused regional campaign - people G can tell are in Boston and people who include Boston geo indicators in their searched phrase (someone in Indiana that searches for "Boston catfish restaurant" will be shown the Boston geo ad).
It is this second group - those who include geo indicators in their search term - that you can neg out of your backup national campaign. In those areas you want to avoid, like Alabama, add Alabama type negative words to your backup national campaign.
Add no Boston type negs anywhere so that both your regional and national backup campaigns are available for hits from Boston geo indicator search phraes and they'll usually go to your regional campaigns because the CTR should be much higher there if you've written regionalized ads (plus the region indicator shows the searcher the region which should also supercharge your CTR).