1. If the product is truly national, like ordering a book, video game, etc - then it doesn't make a difference, AND you still have to run a national campaign to hit the people who Google can't figure out their location.
2. For truly local products, like doctor's offices (even if it's a national lead generation type site), it does help a bit. However, as above, you still need to run a national campaign to catch those whose location can't be determined.
3. Disadvantate: If ANY individual keyword now in 51 adgroups (50 states + 1 national, and maybe 1 content gruop), is disabled, it's disabled in all the groups so you need to keep a close eye on that as it can be a lot more maintainence.
4. Disadvantage: You need to make sure your regional bids are higher than your national bids (the whole bid rank formula at work here) as if your national does too well, your regional ads will never be shown.
In short, you will probably have a slightly higher CTR when the person's location can be determined, but there is a lot more maintainence involved. So if you value your time a lot, it could be more useful to just take the money you'd make doing something else to pump up the national campaign, optimize those campaigns, and save the rest of your time for other projects.
