Which is easier?
Where are going to be when you want the car?
The usual caution you'll get here is to avoid downtown and its almost complete restrictions on non-resident driving (Zono Trafico Limitado). But you can pick up your rental car downtown and drive straight out of town and be on your way. Just be sure the rental office shows you the way on a map. It's not hard.
If you'd rather avoid that anxiety, go to the airport. I don't know if there's a surcharge for renting from there as there is from many airports.
We booked ours from Autoeurope and picked up at the Via Del Gelsimino 11, Florence office that's away from the downtown, to avoid the potential traffic tickets.