If it's a first trip to Italy, I guess you should tick the Milan and Rome (and Vatican) boxes.

Personally, I like Tuscany, we spent a week there some years ago, based in Sienna, and did day trips to other places. I have a summary of my trip here if you're interested. The area is between Milan and Rome making a nice stop over, and easy to fly in and out of the country from America and the two large cities.
@livinguktaiwan/-a-taster-of-tuscany-italy-1599928049002

Venice is also famous, but I have no desire to go; it seems very overrated and too touristy.

Hope you can make a trip sometime, it's a nice country, I like it a lot