I'd recommend you do a quick turn of both Venezia and Firenze - they are tourist traps par excellence and you'll be falling over your countrymen. Now if you must, sure, breeze past Venezia in an afternoon. Can't give you any hints on Firenze, apart from the fact it's overcrowded with tourists, many of them American.
Set aside at least 4 days for Rome, and even that won't be enough. Know of a lady who's been living there for 25 years, and she's still discovering things! You've got to see, at least, the Colloseum, The Vatican Museum (incl. the Sistine Chapel), the Trevi Fountain, the Spanish Stairs (hold on to your credit card; there's a very posh shopping street leading up to the square in front of the stairs - your wife will go mad), the Forum Romana, find excellent restaurants in the Trastevere area and generally lark about soaking up the atmosphere. It truly is an amazing city, one of the greatest on this planet.
Instead of Firenze, my suggestion would be to visit the Napoli area, specifically to see Pompeij and drive the coastal road via Sorrento to Amalfi. Spend a couple of days in Amalfi - small town but loads of of options if you've got a car. It's so incredibly pretty you won't belive your eyes, and the drive along the SS163 is among the best I've ever encountered. Rent a small Fiat 500 and you'll have a real laugh.
Napoli itself is a dump, and a dangerous dump as well - stay sharp.
I should also mention Modena and Sant'Agata - the homes of Ferrari and Lamborghini.
And, of course, if you could find a way to secure tickets for football match, do yourself a favour and go - the Italian league is one of the top 3 in the world. It's not cheap mind, and forget about getting tickets for any of the big matches.
The drive Venice-Firenze-Rome-Amalfi is around 850 km (530 miles). Along the way, near Firenze as it is, you'll be in Toscana. Probably the most gorgeous province of Italy. So many small villages to visit, so much fine food and wine to be enjoyed. Get off the beaten track and just explore that province for a couple or 5 days.
Avoid Milano - it's a heavily industrialised city with nothing much, apart from the cathedral, worth seeing. Stupidly expensive as well.