I rented a car at AutoEurope (via Ognissante) in Florence last September for one week in Tuscany (returned in Grosseto).

GREAT RESOURCE FOR MAPPING AND DIRECTIONS IN EUROPE, WHICH WORKS MUCH LIKE MAPQUEST OR YAHOO MAPS, and tells you which streets are one way, driving directions, etc.:

www.mappy.com (click on small British flag in upper right for English).

I would NOT rent a car unless you are immediately taking it out of the city. There is no need for one in the city, and the historic center is closed to all vehicle traffic except some taxis and buses.

This particular street (Ognissante) is one-way and quite narrow, considering how many people are picking up and returning cars at this location. It is one-way from east to west, so you enter the street fairly close to the river and head slightly northwest.
The staff was fluent in English, quick, and very helpful. They explained to us that rental cars departing this agency (and perhaps others?) are required to follow certain streets upon departure.

In our case we had mapped out the shortest route south into the Tuscan countryside, but they showed us exactly how we had to head north onto the "ring road" to eventually go south. Apparently, you can be ticketed for not following this procedure.

The signs, particularly in Florence, can be difficult to read, as you are almost upon an intersection by the time you can see some (not to mention the confusion of weird intersections and roundabouts).

It is DEFINITELY advisable to have a designated driver with quick reflexes, and the "co-pilot" reading the map and announcing turns, etc. ahead of time.

Upon returning the car in Grosseto, the agency was in a location inside a sealed-off area for outdoor farmers' market! We had to park several blocks away, so be prepared for the unexpected...and to be tailgated mercilessly, regardless of how light the traffic is! We drove all through San Gimignano, Siena, Lucca, Pisa, and took the car on a ferry to Elba and back, and there was often not another car in sight for miles, but if there was one behind us, it would often be less than one car-length away at +/- 65mph.

Best wishes, safe travels, and email me if you have any other questions.