Best way to travel from Berlin to Florence?

Cross-border drop-off fees on car rentals tend to be stiff, although if divided among 5 travelers might not appear that expensive.

Were you going to have a car?? It would have to be pretty large for 5 adults plus luggage.

It would be easy to reach Lake Como without a car. Train to Milan, then train to Varenna Esino. Stay there or ferry to Bellagio. After your time at the lake, take the train from Varenna to Milan and then train to Florence.

Another option by train would route through Munich, Innsbruck, Verona, Bologna.

If you don't want the long train rides, you could fly from Berlin to Milan, train from the airport to the town of Como and ferry to the mid-lake area (Cernobbio/Menaggio/Bellagio/Varenna).

Thank you for your responses. We would prefer to take the train since we have 6 days to travel to Florence and this way we can see the countryside. Do you have any recommendations of interesting stops along the way?

Well, it's all interesting to me, but to each his/her own. You should examine the train routes and see what appeals to you. If Lake Como is a priority, the first option I mentioned above makes more sense. Maybe a couple of days at Luzern, and a couple of days at Lake Como. Some trains stop at Como S. Giovanni where you could taxi to the ferry dock and head to the mid-lake area. Then see Milan on the way to Florence.

Or head straight to Milan, spend the night and a half day to see the sights, then go to Lake Como for a few days. After Lake Como, train to Parma and/or Bologna before going to Florence.

Then again, you included "Austria" in your tags on this thread, so perhaps you'd prefer to go the other way to/through Innsbruck.

There are no wrong answers.

I like spending more time in one place rather than moving every couple of days (especially with group), but this is your trip.

http://www.bahn.de/i/view/USA/en/index.shtml

http://www.fsitaliane.it/homepage_en.html

Jean, I really appreciate your input. Thank you!

Most stops of the direct trains to Switzerland from Berlin are not excessively scenic as those are more cities of a certain size.
If you want a stopover in Germany, you could train from Berlin to Heidelberg and overnight there (just a short hop from the high speed line from Mannheim).
Or go to Munich on day 1, spend 1-2 nights, then go to Como via Zurich.
In general, the north-south main lines are not massively scenic. If you are on a highspeed line, it will be more like on a subway due to the many tunnels.
As you don't have the time to explore the more scenic secondary rail lines, you could as well fly from Berlin to either Milan or Zurich or Basel. You can compare travel times and possible connections on whichbudget.com
I think easyjet flies Berlin-Basel for 30€ or more, airberlin.com to Zurich for €50 or more, and possibly everybody's darling (just kidding) Ryanair to Milan-Bergamo for €50 all-in except luggage.