Rental Car Pickup Location - Florence

We have used the airport location there with no problems. There is at least one (maybe more) near Ogni Santi that you should be able to bypass the ZTLs to reach.

Andrea,
You know already about using the consolidators www.autoeurope.com or their sister company www.kemwel.com for the best prices.
Now, let's get to your question. The choice of pick up and drop off location.
As you know I'm from Florence originally and rent cars there every year. This is my strategy.
First I check the best price on the above websites by selecting the airport location only (Florence Peretola). I always purchase no deductible insurance and the best overall price with the above consolidators, at least in my experience, is either with Europcar or Hertz. I've also rented with Budget in the past, but not through the above consolidators.
Once you have established which company is the cheapest for your period (most likely Europcar or Hertz) then I choose the pick up locations.
EUROPCAR:
Besides the airport, Europcar haste two city locations. One is on Borgo Ognissanti (inside the ZTL), one is on 2 via Forlanini (in the Novoli district, very close to the airport, but without the airport taxes and fees). I'm not afraid of the ZTL, because Florence being where I grew up, I know the streets well. Exiting the ZTL is not a problem, therefore you could pick up on Borgo Ognissanti, however if you return it at the same location, you will go through a ZTL camera (no choice there), therefore you would need to ask Europcar to make sure they place your car in the City website White list, otherwise you'll get a fine. If you return it on via Forlanini, then it's not a problem because it's far from the ZTL. To tell you the truth, I also prefer to pick up on via Forlanini, because on Borgo Ognissanti there are too many foreign tourists in line to pick up the car and I the wait may be long.
HERTZ
If the best price is with Hertz, besides the airport, they have two city locations. One is also on Borgo Ognissanti, the other is on 53 via Del Sansovino. The Borgo Ognissanti location, unlike Europcar, can be reached without going thru the ZTL camera, however you need to know EXACTLY how to get back there to avoid them and that only way is from via di Borgo San Frediano and Ponte Vespucci. A safer option if you don't know Florence too well, is to return on via Del Sansovino. Once again picking up is not a problem even on Borgo Ognissanti.
AVIS-BUDGET
This rental company is located only at the airport and on Borgo Ognissanti (exactly across the street from Hertz). They rarely, if ever, have the cheapest price so it doesn't really matter.

Thank you Linda and Roberto! I always use Auto Europe when I rent. This year I will need a rental in Italy and Austria. Roberto, I was hoping you would weigh in and I appreciate your detailed information. My fear is taking a wrong turn (it happens!) and ending up in the ZTL. maybe it's worth the time and cost of getting to and from the airport to rent there? Decisions, decisions...

Picking up the rental at the airport will cost you more because of airport taxes and fees.

If you intend to pick up the car upon landing, for example to go out somewhere in Tuscany, then it might still make sense, because you would spend more in rental fees, but you would save the taxi fare into the city. I think the airport taxes add about $30-40 to a weekly rental. Since the taxi into the city is about €20-25, then it's a wash.

But if you plan to be in the city, then rent a car from the airport at the end of your stay, then you would have to incur taxi fare to the airport (which is high, in my opinion, considering the airport is only 3 miles from downtown), plus you would incur higher rental fees because of airport taxes.

If you are staying downtown when you rent the car, the best strategy is to rent the car on Borgo Ognissanti (all companies are there). You can walk to it from the city center. The cars for Europcar are delivered to you on Piazza Ognissanti on the eastern end of Borgo Ognissanti (across the piazza from the Excelsior Hotel). If you select Hertz or Avis or Budget, the rental cars will be at the Garage Europa which is on western end of Borgo Ognissanti, almost at the corner with Via Curtatone. Either way you drive your car west on Borgo Ognissanti (it's a one way street), you go straight all the way, the street changes name after the intersection with via Curtatone and it's named Via Il Prato. After 200 mts you reach the intersection with Viale Rosselli (big city gate tower in front of you), where you have no choice but turn right. It's really simple and it's impossible to be fined because you are allowed to drive there and there are no cameras.

If you return the car in Florence, then there is the danger you might accidentally get lost trying to get back to Borgo Ognissanti and get zapped by the cameras. There is a camera on Lungarno Vespucci just east of the bridge, and across the river (if you come from that direction) there is another camera on Borgo San Frediano just east of Piazza de' Nerli.
To avoid the stress, just return the car far from the ZTL.
HERTZ: via del Sansovino or the airport
EUROPCAR: via Forlanini or the airport
AVIS-BUDGET: airport.
You don't incur airport taxes if you return the car there, you do only if you pick up the car at the airport.

In other words, the danger is trying to return to Borgo Ognissanti when you bring back your car, not when you exit the area after picking up your car.

We are actually traveling by train from Verona. We will spend 4 nights in Siena (not too far from the train station) and 4 nights at an Agriturismo in Pontassieve. I originally planned to pick up the car in Siena and return in Florence before taking the train to Varenna. In that scenario the location options were very limited. Any other suggestions are welcome.

• If coming from Verona you are going straight to Siena area after Verona, without staying in Florence first, I'd rent the car in Verona and drive to Siena (if you plan to have a car in Siena for day trips in the area) and not bother with the trains at all. If you plan to stay in Florence a few days before heading to Varenna, then return the car in Florence, stay a few days, and go to Varenna by train (via Milan).

• If, coming from Verona, you plan to stay in Florence for a couple of days first, then it's best to travel by train and at the end of your Florence stay, drive away to Siena with the car from Borgo Ognissanti. If after your Pontassieve stay you go straight to Varenna, I wouldn't bother to return to Florence to drop the car. I'd drive to Lecco (just before Varenna) and drop the car there. Lecco has both Europcar and Hertz offices. Then from Lecco to Varenna you can take the short train ride or even a bus (even a taxi, but it might cost a bit more).

Roberto, you are a genius! Auto Europe is having a sale and I was able to book a car from Verona - Lecco for 8 days including CDW for $301. My one week rental with a deductible was $36 more than that! They also waived any one way fees during the sale and it includes the VAT.