What is best way to get to Citta di Castello?

It’s Castello not Costello.

You will probably need a car once there, since it’s a small town. So the fastest way is to rent a car, no matter which airport you use.

I don’t know where you fly from. The closest airport is Perugia but only RyanAir has flights to Perugia, and very few. The second closest is Florence. The next is probably Rome, which is also the largest, therefore with the most flight options.

If your sister can provide the car, maybe you don’t need to rent one. There is SULGA bus company that connects Città di Castello to Rome (even to the airport). But only one bus daily each direction.
The other option could be a train to Arezzo, then the TIEMME bus to CDC. But only two buses a day each direction.

Umm, Your sister cannot answer these questions?

Thank you for the information regarding getting from Rome to Citta di Castello. I'm flying out of San Francisco. I am looking into the Sulga bus from Rome Airport to CdC. I will be renting a car when I get to CDC. I'm also looking into bus to Perugia then renting a car to CDC. Since I am traveling solo, I don't want to do a long drive by myself from Rome.

I will be visiting my sister, who is currently traveling, and does not have the information I need. That is why I appreciate your helpful suggestions!

Rent a car in Foligno (Europcar) or Spoleto (Hertz, Avis)