Welcome to the RoadTrip America Forum!
For me it really comes down to instincts. If I'm in an area that I don't feel safe in, then I don't consider lodging there. In earlier days, I did occasionally stay in areas that weren't the most desirable, but even then I didn't have a problem. Now, however, I'm more diligent before settling in for the night. It can be rough, especially if it has been a long day, to keep the guard up, which is why I recommend stopping well before reaching the point of exhaustion to keep your wits about you.
This current thread is definitely a good place to start.Any other advice for a 20-something female first time road tripper that you might have would be similarly appreciated. Thank you!