Bright and early is a good time to tackle perhaps the single largest sightseeing project in Rome. St. Peter’s Basilica opens at 7 am, so get in there for a gaze at the largest and one of the most over-the-top church interiors in Christendom. The top highlights here, of course, include Michelangelo’s Pietà,the Virgin Mary holding the dead Christ, and Gian Lorenzo Bernini’s elaborate bronze altar canopy (known as a baldacchino). At 8 the dome opens, and to save time (and your feet) you’ll want to spend a couple of extra euros to take the elevator up for some sweet views out over the city. Then, around 8:45 am, head out into St. Peter’s Square and bear left, following the wall to the Vatican Museums, an extensive, complex maze of rooms and art collections that alone could take weeks to absorb. You’ve got maybe a couple of hours, so you’ll want to stick to the absolute musts. That would be the Pinacoteca, the painting gallery whose stars include Raphael’s Transfiguration; the Raphael Rooms, adorned by that painter for Pope Julius; and of course the magnificent Sistine Chapel. Before leaving this side of the river, you’ll want to stop at hybrid classical-Renaissance Castel Sant’Angelo, which started out as an imperial tomb, was converted to a Roman fortress, then much later a papal castle and prison.
Read more in my post Rome in One Weekend? Sì, Signori!