Well, I have been to Rome four times so far; I didn’t try it a lot, it simply happened! Brief visits mostly but I think that after so many times, I got at least the basics of the city.
Fly in/out
Two airports nearby, Fiumicino and Ciampino. Rome is one of the connecting point for the majority of airliners so you can easily grab a flight from everywhere, any time you wish.. To get to the city centre there are shuttle buses and taxis (Warning: There are fixed fares! But some drivers will ask for more,- especially during nighttime. Don’t bargain anything, just call the police.) Train connection is only available from/ to Fiumicino.
See & Do
Only in Rome is it possible to understand Rome- Goethe
Rome is a kind of open museum; just walk and admire. I would suggest to start over from piazza del Popolo to Spanish steps, via Condotti (keep your credit cards away from your wife’s sight!), Fontana di Trevi (don’t forget to make a wish!), Pantheon, piazza Navona, piazza Venezia, Forum Romanum (even more impressive during nighttime!), Colosseum, Circus Maximus, Tiberina, St Maria in Trastevere and Castle St Angelo. Believe it or not can be done in a day as long as your are not a lazy walker. Worth to have a visit to Vatican museum but be prepared to wait a bit (or longer!) in the queue.
Eat & Drink
Food for Italians is a ritual; quality on their tastes is guaranteed! Yet, on the city centre there are places for tourists where the norm is not being followed. Make a bit of search on your own before booking a table. Here are few recommendations by me but I am pretty sure that there are even more options. Pizzeria La Montecarlo, Antica Osteria Brunetti & Da Armando al Pantheon. Make sure to take some coffee in Tazza d’ Oro and a drink in Salotto 42.