I did exactly this a few years ago from Istanbul. I was there for a second weekend on a mileage run when Turkish first started LAX nonstops.

Not wanting the entirety of the second weeekend in Instanbul, I flew to Rome for the day. Really late flight back so had plenty of time.

I recall I did a Hop-on/Hop-off bus but ultimately just hopped off and walked the rest of the visit before heading back to the train station to go to the airport.

It was great!