On our small group tours to Italy, we have found the best hotels Rome for us.  Our criteria is location, comfort, value and ease of getting to various attractions.  Location is particularly important in Rome.   I prefer hotels near the Termini train station (both of my best Rome hotel picks are near the train station) and let me tell you why:

For those coming or going to or from Rome by train, staying within walking distance to the train station saves on taxi fare both ways.      

Adjacent to the train station is the main bus station.  Travelers can get ANYWHERE in Rome from the main bus station.  Plus, Rome buses are known to be extremely crowded.  However, when getting on a bus at its origination point, travelers are neraly always guaranteed a seat.

Subway:  All subway lines in Rome meet at the train station.

Restaurants:  Some of our favorites are close to the Termini train station.

Closeness to Attractions:  The Colosseum and Forum are within walking distance.  As mentioned before, public transportation options to other options are best from Termini station.

Safety:  Usually in cities, I stay away from train stations, they can be a bit gritty.  However, Rome has made a great effort to make this area safe and clean.

Here are The Professor's picks for the best hotels in Rome.

Albergo Nord Nuova Roma:  Good size rooms, excellent breakfast, decent size lobby, pleasantly decorated make this one of my favorites.  I like this hotel for it's rooftop sitting area.  It's perfect to have a snack or cocktail at night and view night time Rome.  It is rated as a 3-star hotel, but it is really a 4-star.  The reason the hotel prefers a 3-star rating is because government regulations dictate those on government business must stay in a hotel rated 3-stars or lower.   Hotel Nord is 4-stars on all levels but since they like to attract steady government business travelers, they keep their rating at 3-stars.  However, the travelers gets a 4-star hotel at a 3-star price.

Hotel Massimo D'Azeglio:  About a 2-minute walk from the train/bus/subway station, this is my pick for the best hotel in Rome. At 4-stars it is comfortable and quiet.  It has a wonderful lobby and small bar for relaxation after a long day.  The rooms are large, by European standards.  The staff is good at what they do and I always enjoy my stay at the D'Azeglio.