As as has been said before, go with your gut feelings!
I check out the entire profile first before I respond. Then I try to start some sort on conversation by asking about them, why they travelling etc. In some cases, I have even gently suggested that they work on their personal profile! Remember that you have 24 hours to finally accept or decline a booking. See how the conversation goes first via the AirBnB email system to guauge the validity of the person. I find that if I have quite a bit in my responding email to them and they don't respond, nada is going to happen anyway. Those that do respond with lots of "inside" info, and share well, these guests are generally all fine (I've had no issues). My personal preferences are women, couples, or travellers with children - this also helps me make a quick decision as solo men are usually declined by me. So that I don't get too penalised by AirBnB for not accepting or declining a booking, I leave it for a while before I do this, and then I have found that the booking request expires anyway as the guest has not finalised from their side - the booking request just expires. Some people really are authentic first time guests and first time they are using AirBnB, so gently help them too.
Yes, there may be a penalty for cancelling a booking after its accepted if you suddenly regret the decision - thats up to you as it will affect your rating, and, you will have a financial penalty, but if something really concerns you, go with your gut.