I do the trip regularly.
Shop the airfares with different airlines. Many times you can do an "open jaw" (fly into one city and back out of another) with little added expense. If you're stuck having to do the same city both ways, look at the cost of a Round Trip (RT) ticket on a European airline (like Easyjet) and throw away the return - a RT is often much cheaper than a one way.
Cellphones: depends on what you have. ATT generally works well both here and abroad, but you will pay for the privilege. I am loving my Verizon 4G world phone - it works here, Europe, Asia, and South America without a problem. If you don't have a world phone, Verizon will rent one. Get the international data pack for either ATT or Verizon and set the phone up for minimum over-the-air data usage (use wifi at the hotels whenever possible). TMobile and Sprint have horrid international data plans - TMo used to have a better voice roaming plan, but I've dumped them due to the data costs.
Best if you can get a local SIM card. Rules differ by country - I have a TIM card for Italy that I keep active, I've heard some folks talk favorably of HolidayPhone.com for Paris, and I have used a local Vodaphone SIM in Spain. In London, there are vending machines at the airport for SIM cards - I've not seen that in Paris or other countries (some countries have identification rules for folks buying SIMs).
Renting a car is straightforward. While I have a really good corporate deal, I'm going to assume you don't... in which case I highly recommend a US-based broker like AutoEurope. I have had excellent service from AutoEurope, and great pricing to boot. Be aware that some rental companies in Europe have different rules for Italy.
You really want to avoid driving in the cities. Seriously, take the train and public transit. Parking is expensive (hotel at Karlsruhe was over US $20 for the night last month - Paris is much higher). It is easy to arrange a car rental pickup in-town or at the outskirts. Also, taxes on airport car rentals are much higher... I sometimes save money by taking the train into town and getting a rental there.
London and Paris have "luxury taxes" (air passenger duty) that they assess on flights leaving their countries. Paris is less than London, Brussels is less than Paris, Spain and Italy were (last time I checked) much more reasonable. Better to fly into Paris and leave from somewhere else.
All that said, the countryside is mighty fine. In France, I've had excellent luck from
http://www.chateauxhotels.com/ which is a booking agent for hundreds of small, local hotels outside of the major cities. Some of my most memorable stays were hotels at listed there. If I recall, there is a similar site for Italy.
Where to go depends on season & what you want to see. For Spring, Provence in France is really nice, as is Tuscany in Italy.
Wine country for spring & summer. Besides spring, fall is nice for Tuscany in Italy (it gets very crowded in the summer, likewise the coast of France - Nice, San Tropez - is very crowded in summer). Paris is full of Americans in August - the French go on holiday that month. Personally, I like Vienna, Budapest, and Prague in the late Novemeber/all of December winter when it's cold & crisp and the Christmas markets are out. Each season is different.
April will have some chilly nights & spring-like days. April is tulip season in Holland (and Istanbul). You'll find flowers out in the south of France.
So much to recommend - if you can narrow it down a bit, can probably help more.