How to experience best of Eternal City in one short weekend
You could take multiple lifetimes to explore Rome. I've been here for two months, and I'm still barely able to comprehend what a truly magnificent place it is. The absolute richness and density of the city make it difficult to plan a quick trip here. Of course, there are the "biggies," the places people tell you would be crazy to miss: the Colosseum, the Vatican and the Roman Forum, to name a few. However, you would be remiss if you spent all of your time waiting in line at big attractions instead of really exploring Rome.
For first time visitors to the city, I recommend striking a balance: one "main attraction" a day, followed by plenty of exploring and eating. Rome is, after all, in the details.
Colosseum and Forum Tour
For around 30 euro per person, you can get a tour of both the Colosseum and the Roman Forum. It will take most of the morning, but it will be worth it. The Ancient Roman history will provide an excellent backdrop for the rest of your trip.
Head down to Testaccio to explore. This neighborhood used to be home to the slaughterhouses of Rome, but now it's a bustling district full of good food and often modern art. The Testaccio Market is a great place to walk around — you'll find stalls selling fresh produce and meat, as well as kitchen supplies and clothes. Get lunch from Mordi e Vai, a stand with some of the best panini in Rome.
Head back to your hotel, hostel or Air BnB and take a little rest. You're probably near the center, so now wouldn't be a bad time to do what I call the "piazza walk." Starting at Campo de Fiori, make your way to Piazza Navona and then the Pantheon. Get dinner at Armando al Pantheon, probably the last quality restaurant in the area. The rest of the night is up to you, there are plenty of bars throughout the city for you to satiate your thirst. If you want to take your drink to go, ask for "plastica."
Vatican Museums, St. Peter's Basilica Tour
If you want to see the Vatican, and you're going in tourist season, book a tour. You will save so much time waiting in line. Even if you aren't into art, these museums are necessary to see. You'll see Michelangelo's "Sistine Chapel" and Raphael's "School of Athens," among many other breathtaking works of art. The Basilica is also absolutely full of amazing art and is worth a visit. It'll be a long day, so make sure you get a caffe and a cornetto first.
Walk along the Tiber until you hit Trastevere, turn right. Trastevere is where I live now, and while most of the year it is absolutely full of tourists, it is still incredible and necessary to visit. You must try Roman pizza while you're here, and one of the best is at Dar Poeta. Grab a pizza and a beer for lunch. Walk a little deeper into Trastevere and find the Piazza di San Cosimato and get gelato at Fatamorgana, where they have fresh gelato and amazing favors. Keep walking around, looking about as you do. Trastevere is one of the most picturesque neighborhoods in Rome.
Wander over from Trastevere into the Jewish Ghetto. Walk around, look around and eat dinner at Nonna Betta. Nonna Betta has Roman as well as Roman Jewish classics. Try the artichokes. Next hop on a bus or hail a cab and go see the Trevi fountain at night, toss in a coin to ensure your return to this magical city. From there, walk to the Piazza di Spagna, climb the Spanish Steps, and see Rome at night.