We will be picking a car up in Venice and dropping the car off in Florence.
Are there any recommendations on places that are easy to access for both pick up and drop off locations?
Standard advice here is: drop off at Florence airport car return and take a taxi into historic Florence, train station, or wherever. Airport is close to town and small, people have reported no problem returning cars there.
Reason for this is that historic Florence is covered by Zones of Limited Traffic (ZTL's) and travelers trying to return cars at the train station or other locations within the historic center have frequently unknowingly made incursions into the ZTL's, which results in hundreds of dollars of administrative fees (on your credit card) and fines (not on your credit card) showing up after your return home.
Here's more on the Florence ZTLs and why you don't want to drive into the historic center, even to return your car
http://www.florence-on-line.com/maps-of-florence/florence-driving-map-ztl.html
I second the advice to drop the car off at the Florence airport. You don't want the hassle of trying to make your way into and around the city.
No question Florence airport is a better option. even if it costs alittle more to drop off. you do not want to ghet fined in Florence. they have street cameras everywhere and if you follow this helpline you will read that many have gotten caught with huge fines that come via rental co since they have your addresss contact info.Save the stress and horrible traffic in FLorence proper.