The Duomo. When I would get lost walking home at night, I would get oriented by asking passers-by "Dove il Duomo?". That little bit of info always go me back on the right track. Should that have been: "Dove il Duomo è?"
Ahhh, this is to Florence what the Eiffel Tower is to Paris. You really need to see it in person to appreciate it. It just glows at sunset. When I stayed there I made a point of looking at it from a little hill where I was staying every night as the sun went down. Just didn't look real.