Are We Crazy? Rome, Florence, Cinque Terre and Lake Iseo/Orta in 11 days?

Do you have 11 nights in Italy, which would amount to 10 full days? If so, I think this could work, but I'd vote for omitting Cinque Terre and only going to one of the lakes - too rushed, otherwise.

We have 10 nights and will only visit one of the two lakes, we are leaning toward Iseo. We will rent a car in Milan to take to Lake Iseo and to the airport. Thank you!!!!

Do you think Cinque Terre will be too busy first full week of May?

I would say, yes, you're crazy. Let's map out a potential itinerary. I'm assuming you're traveling by train, but for the sake of this discussion it doesn't matter that much.

Day 1 - arrival in Rome. It will probably take most of the morning to get into town and get settled in your hotel. Jet lagged. Afternoon and early evening in Rome, then probably to bed early.
Day 2 - Rome. Still jet lagged.
Day 3 - Rome. Probably still somewhat jet lagged.
Day 4 - Depart for Florence. It's a short train ride but it'll still be late morning before you're settled in. Afternoon and evening in Florence.
Day 5 - Florence.
Day 6 - Florence.
Day 7 - Depart for Cinque Terre. It's about 3 hours by train from Florence, so you'll use up the morning and probably part of the afternoon getting to your destination. Part of an afternoon plus an evening in Cinque Terre.
Day 8 - Cinque Terre.
Day 9 - Depart for Lake Iseo/Orta. Looks like the best case train route is over 5 1/2 hours, possibly as much as 7 hours, so figure that travel eats up the whole day. Evening in Lake Iseo/Orta
Day 10 - Lake Iseo/Orta. Leave before dinner for Milan (assuming you have a morning flight home - it's 3-4 hours by train)
Day 11 - Fly home.

So in this itinerary, your 11 days gives you:
Rome - 2 1/2 days
Florence - 2 1/2 days
Cinque Terre - 1 1/2 days, which is
Lake Orta/Iseo - 1 day
No matter how you redistribute the days, you're losing a lot of time to travel.

If it were me, I'd probably omit Cinque Terre. That eliminates the longest legs of travel.

Also, though I know you like the idea of going somewhere off the most heavily beaten path, visiting Lake Como instead of Lake Orta might make it possible to avoid an overnight stay in Milan before you fly home (depending on how early your flight is) since Lake Como is closer to Milan.

With those changes:

Day 1 - Arrival in morning. Afternoon and early evening in Rome, then probably to bed early.
Day 2 - Rome
Day 3 - Rome
Day 4 - Rome
Day 5 - Travel in morning. Afternoon and evening in Florence
Day 6 - Florence
Day 7 - Florence
Day 8 - Morning in Florence; then travel to Lake Como (around 3 hours). Late afternoon and evening in Lake Como
Day 9 - Lake Como
Day 10 - Lake Como. Possibly travel to Milan in the evening if flight home is early.
Day 11 - Fly home

Now we have:
Rome - 3 1/2 days
Florence - 3 days
Lake Como - 2 1/2 days

You can adjust the amount of time in each place, but

I wouldn't say "crazy", but IMO this Itinerary is far too ambitious for the time frame. Does that 11 days include your two flights days?

My suggestion would be to visit Rome and Florence, and choose either one of the lakes OR Cinque Terre. Rather than Iseo / Orta, my preference would be either Lago di Como or Lago Maggiore as those are both well served by public transit and easy to reach.

Keep in mind that with car rentals in Italy, each driver will require the compulsory International Driver's Permit, which is used in conjunction with your home D.L. You'll also have to be vigilant to avoid the ZTL (limited traffic) zones which exist in many Italian towns. Each incursion will come with a hefty fine! There are also some potentially expensive caveats when using trains and other public transportation, so be sure that you're up to speed on those too.

Yes, the Cinque Terre probably will be busy in May. If you decide to stay there, it would be a good idea to get accommodations booked soon!

I’m not clear what you mean by”Lake Iseo/Orta.” They are two different lakes, not terribly close to each other, and probably harder to travel between than you may think. If you decide on Iseo, be sure to check out the area just to its east, which is full of rock engravings. They range in age from pre-historic to 16th century.
All told, for a first trip, I’m inclined to vote with the posters who recommend Lago Maggiore. There is quite a bit to do and see there, and the connection to Milan is fairly easy.
One more heads-up. If your trip includes May 1, be aware that it is a national holiday, with all that implies; crowds, closures, reduced transportation,etc.

Your revised itinerary looks great. You skipped Venice, but can do Italy again later.

Since you flying out of Milan, stay on Lake Maggiore. Ranco on the east side of the lake is lovely and close to MXP.