Skip Pisa. (personal opinion)
You can do Sienna and Lucca by bus. You can rent a car, and driving is fine, but parking is THE problem, especially in Florence. Rent only for one day at a time, if rates are similar for 2 day rentals. Why pay to park at night, even IF you can find a spot? We wound up paying for overnight parking in the same rental garage as the rental car!
A small van tour for wine country is ideal. They do the driving, and you do the sightseeing. (and wine tasting)
If this is your 1st time in Venice, stay in Venice. We stayed at the Best Western in Mestre once (for an early air departure, before the airport hotels were built). The hotel is great. They have 1€ tickets for the train at the front desk. It's ideal for the train, but it's a pain at night traveling from Venice after a great meal and liter of wine. Spend the bucks for Venice. It's worth it.
Florence is a great base for day trips by train. Bologna, Arezzo, Perugia, and Orvietto are done easily.
Day trips from Venice include Padua (skip Monday morning) and Verona.
Yes, -planning is a good part of the fun.
We always use the Star Alliance for out trips. Take connects in Munich over Frankfort, when available. Much simpler.