dyl - many of us are more lucky (or blessed) than we know.
Here are some suggestions to think about. First, don't stay in a motel/hotel that doesn't have a lighted drive in style check-in. Look on the internet to choose the accommodations that look the most safe and that are in a good area of town, before you leave.
Next, after you check in, unload your wife and bags before parking your car. Make sure your wife has a gun and knows how to use it. Have her stay in the locked car until you make all the arrangements and can see that it is safe for her to get out of the car and go to your room.
Third, don't get a room that is too easily accessible from stairwells or elevators. Make sure the room has substantial security locks and a fire alarm. Check the windows or outside balcony to make sure it affords no easy access to outsiders.
In addition to your gun and your wife's gun, make sure you have a backup. I personally have my wife carry the snub 357 and I carry a High Capacity semi-auto with four (min) magazines and my LCP on my ankle with three extra mags for it. And, I carry a good tactical folder such as my SOG Aegis Folder.
Or, my Ontario XM1
Finally, remember that situational awareness is paramount in EVERY aspect of your life. It is YOU that is responsible for the safety and welfare of your wife and/or children. So, instead of just walking into scary or dangerous situations and then being surprised and thankful that nothing bad happened, you need to think ahead and be watchful for trouble before it happens. And you should have already practiced various scenarios and made decisions about what you would do in this or that circumstance.
Be in tune with everything that is happening around you at all times. Know your weaknesses as well as your strengths and be prepared to do whatever is necessary to provide safety for you and your family. It's YOUR duty!