Road trip from Barcelona to Florence

In EU countries all forms of public transport are safe and comfortable enough.
1. The most inexpensive form of travel is always by bus, local or long-distance. There is a reasonable long-distance bus network throughout the EU though nowhere near as extensive as the rail network. Journeys are almost always slower than by train.
Long-distance bus operators include: 
https://www.eurolines.de/en/home/
https://www.flixbus.com/
2. Travelling by train can be pretty inexpensive, especially if you take advantage of online advance tickets for high-speed trains or use the slower local trains. All EU countries have railway websites with English language pages.
Spain: https://www.renfe.com/es/en
France: https://www.sncf.com/en
Italy: https://www.trenitalia.com/en.html with a second high-speed train operator on some routes https://www.italotreno.it/en
3. Renting a car can give you the ability to stop where you want but it's not a cheap option. As well as the cost of rental, a potential premium for taking the car out of the country and a hefty premium for one-way hire you need to factor in:
a) the cost of fuel. Fuel prices in Spain, France and Italy at the time of writing are roughly 1.40 to 1.50 euro per litre (about 2 pints), the equivalent of 5.60 to 6 euro per gallon).
b) Time and hassle finding parking and parking costs (never cheap).
NB: Cars are banned or restricted in the historical centres of many cities, towns and even villages (e.g. the Cinque Terre villages). These areas can be (and often are) monitored by CCTV (especially in Italy) with the automatic fine taken from your card via the rental company. 
If I were travelling from Barcelona, Spain to Florence(roughly 700 miles) I'd go by train, visiting at least Perpignan, Nimes, Aix-en-Provence, Genoa and Lucca on the way but you may well have different preferences. :-)