To start with where to stay, if you want to enjoy a lively neighborhood, very populated by locals and artists and close enough to the main attractions I would recommend to stay in Trastevere, which is a very nice area just across the Tiber River and a few minute walk from the Foro Romano and the main historical center. Last time we stayed in a lovely airbnb owned by a very nice woman (who worked as a scientist in Baltimore for a while) that is very convenient to the main piazza Trastevere, where all the restaurants are. It used to be an old convent!
One restaurant that I would absolutely recommend is this one, very famous but still very cheap and good… “Da Enzo al 29”. The only problem is that it has very few table and sometimes you have to go there early (7 pm for Italian time) and wait in line because they don't accept reservations…
All around that area there are many “trattorie” or “osterie” that cook the traditional roman dishes… bucatini alla amatriciana or alla carbonara, carciofi alla giudea, saltimbocca alla romana… they are all good!
Il Grappolo d'oro is another restaurant that we tried last time was near Campo de’ Fiori and that was very good (another very nice square, in the middle of the historical area).
As for the things to do... it’s so difficult to select! But THREE DAYS are enough to have an idea: I would suggest to do the “Roman” Rome one day, then the “1400-1800” Rome the second day and then maybe the Vatican and the hills/park the third day, so that you could also have a glimpse of the chronological “layers” of Rome and it’s architectural wonders!
ANCIENT ROME
As for the Classic Rome, of course she shouldn’t miss the Colosseo and the Fori, but also the Palatino where Roma was actually founded (it’s the same ticket). It’s very convenient to reserve the package online so that you can skip the long lines… here’s where you do it:
Across from the main Foro there is also a good pizzeria for lunch.
The whole area is full of other Roman ruins… the Circo Massimo, the Colonna traiana… but I am sure a good travel book will guide them through it. Coming from Trastevere you can also see the “Bocca della verità” (Mouth of Truth) and take a detour to the Terme di Caracalla and the Cathacombs.
RENAISSANCE ROME
As for the “Centro” di Roma, they can just walk on the cobbled streets between the Tiber and the Pantheon, Piazza Navona, Montecitorio (where the Italian parliament is), Fontana di Trevi, Piazza di Spagna and all the way to Campo de' Fiori… all very beautiful, full of stores and restaurants but also very crowded! You can’t escape the tourists unless you go there at night
From Piazza di Spagna you can walk up to Villa Medici, Terrazza del Pincio (for a nice view of the centre) and Parco di Villa Borghese, which is a beautiful park where she can also visit a nice at museum (a private collection) in the wonderful palazzo Borghese.
THE VATICAN AND THE GIANICOLO
As for the third day, I would start for Piazza San Pietro and the Vatican, do the incredible Musei Vaticani (where the Sistine Chapel is), Castel Sant’Angelo and maybe take some time to walk also to the Colle Gianicolo, where there are amazing old palazzi surrounded by parks and the best view of Roma!
From the Fontana dell’Acqua Paola she can walk down back to Trastevere, and it’s a nice hike that not many people do.
Rome, as chaotic as it may seems, is pretty safe and easy to walk around, and also the public transportation works well. The only problem may be the hundreds of “road works” across the city, because everywhere they dig… the find something!
The best times to visit Rome are spring and fall, when it's less crowded and it's not hot. As all touristy places, the price range of things is pretty wide… the best would be to try not look too naives and unprepared because Italians tend to take advantage of it, especially Americans… and if you can understand and communicate a little bit in Italian, it’s much better! 😉
For this reason, here’s an agency that a friend of mine recommended me once -tour the city with a local person (you can even do the Vespa tour!):