I fully recommend booking the Guest House. We booked a double room, but due to an opening we were upgrated to a big 4-person bedroom for free. The rooms are beautiful, bright, modern and have newly renovated bathrooms. We are quite particular when it comes to cleanliness in hotels and felt perfectly comfortable, as the room was absolutely spotless.
Francesco, the owner, was a very friendly and helpful host, who took a lot of time to recommend the most important sights, tobgive us some tour ideas and to suggest some fantastic italian restaurants all over the city.
We were also very happy with the location as the guest house is just 5-10minutes away from the San Pietro basilica and square, another 10minutes from the Vatican museum including sistins chapel or the Sant'Angelo castel. From there on you can cross the Tiber, where you find yourself in beautiful romantic narrow streets leading you within 15min to Piazza Navona and further sights of the inner city. The Colosseo and Foro romano can be easily reached by a bus without having to change buslines, the bus station is just 3minutes from the guest house.
The area felt totaly safe for 2 women to walk late in the evening. The guest house is near the railroad, we heard the trains in evening from the room, but only a little, it was definetly quite enough.
We would surely book Leonardo Guest House again.