Two days in Rome is enough for the big sights if each morning has one timed ticket and the afternoons are spent on foot. Day 1 is ancient Rome and the centre: the Colosseum at 8.30am, the Palatine and the Forum, lunch in the Jewish Ghetto, then Piazza Navona, the Pantheon, the Trevi Fountain and the Spanish Steps at sunset. Day 2 is the Vatican: the museums and the Sistine Chapel at 8am, St Peter's after lunch, then a walk over the Janiculum Hill and down into Trastevere for the evening.
Keep the Colosseum and the Vatican Museums on different mornings. Both are best at opening, they're on opposite sides of the river, and each wants half a day. You'll walk 7 to 8 km a day, with the Metro (the subway) only to reach the start: line B to Colosseo, line A to Ottaviano or Cipro.
Day 1 works on any day. Day 2 is best Tuesday to Saturday, because the Vatican Museums close on Sundays except the last one of the month (on a Monday, skip the Tempietto, which is closed). In winter (25 October to 28 February) the Colosseum and Forum stop admitting at 3.30pm. Prices are full adult prices at November 2026. For everything else worth doing, see the best things to do in Rome; with only one day, follow the 1-day plan.