5 Nights in Italy

As Mary noted, Lake Como  is a very convenient choice and you don't need a car.  You can ferry around the lake to the various towns, and it is a very relaxing stay. 
We stayed in Bologna two years ago, and found it very charming and, of course, the food was excellent.  The trains from Milan to Bologna are convenient, and you can fly from Bologna to London easily.  There are also very easy train travel from Milan to Parma, Modena, and Bologna. Ferrara is close to Bologna and Ravenna is a little farther.  You could stay in Bologna as a base and visit the other cities in the area, of break up your nights between two of them. 
Another suggestion is Tuscany.  You can reach Florence in about 2 hours by train from Milan, and pick up a car there to drive to anywhere in Tuscany.  We stayed in Castellina in Chianti for a week and then drove down to Montepulciano for another week.  We took day trips to the various Chianti villages, Siena, San Gimignano, and Volterrafrom Castellina; and Perugia, Assisi, Montalcino, Orvieto, and Pienza from Montepulciano.  We drove through Tuscany to Pisa and stayed a final night, before flying home through London from there.  Castellina in a beautiful little village and the people there are very friendly.  There are some very good restaurants in town, and the wine available is excellent.
Lots of good choices for your 5 nights.

Before you make any final decisions, check flights to the UK using the reliable www.skyscanner.net  Book on the airline's own website but make sure you factor in the cost of checked luggage, plus size and weight limits for both checked and cabin bags. If you've got several bags and/or heavy bags, you may find you can't use the excellent budget airlines such as Easyjet and Ryanair, so you'll be stuck with mainstream airlines such as BA. That will limit your choice of airports too.
> Should we head towards Florence or Venice?
Neither, in my opinion. Why go to the busiest and most tourist-popular (year-round) places if you've already visited them?
From Milan you have several options:
1. Drive (or take the train) to Bergamo. Base yourselves there (plenty of hotel options) explore its lovely, historical Citta Alta (upper city) with its two funiculars, try some of its fabulous food and walk in the surrounding countryside.  For day trips from Bergamo you can drive or take the train to lovely a) Varenna and Lecco on Lake Como and to b) Brescia, which is full of history and has a truly fantastic museum which incorporates two Roman villas. You can drive or take the bus to a) Sarnico on the beautiful but much less-visited Lake Iseo and b) drive or take the tram to nearby Albino  (worth a wander for its architecture) then bus from the tram station to wonderful Clusone, a 'painted city' in the mountains with many Medieval murals on its historical buildings. 
You can fly back to the UK from Bergamo, Milan Malpensa or Milan Linate.
2. Drive or take the high-speed train from Milan to Bologna which has more than enough history and superb food to occupy you for 4 days. For a day trip, drive or take the train to Ravenna, a stunning UNESCO World Heritage Site with many magnificent Byzantine mosaics. 
There are some UK flights from Bologna airport but it would be easy to return to Milan (Linate or Malpensa) or take the high-speed train to Venice (Marco Polo or Treviso) 
3.  Drop the car in Milan and take the high-speed train to Venice. Either base yourselves there or stay in Mestre, a much cheaper option with its own interesting historical centre and easy access to Venice by bus or train. From either place take the train to explore a) buzzy and hugely historical Padova ('Padua') and b) historically-fascinating Verona. 
Fly  to the UK from Venice.
Plenty of choice but, if it was me, I'd drop the car in Milan and choose Bergamo for its lovely Citta Alta, its many easy daytrips by public transport and its ease of access to Milan airports. :-)

Florence and Venice are both nice and you can fly home easily out of either airport-much easier than Rome. I'd spend two days on lake Como if I were you. Ive been three times.