I like to get somewhere around 300 Euros when I leave, and my husband and I each carry half of it. Then I use in country ATMs after that 300 is gone. I use cash for most everything except big-ticket items like hotels, long distance trains, etc. I like to have that 300 Euros when I arrive in case of any weirdness. For example, on my last flight to Madrid, we landed before 6AM and most of the airport service areas were closed - restaurants, etc. It was basically a ghost town. While I could probably have found an ATM somewhere, all the ones I saw were in closed areas. Without cash, I would have either had to hunt down an ATM, if possible, or wait until the main sections opened. Instead, I had my cash for the express bus to the train station and was on my way. Wouldn't have been a disaster - just wait for awhile or scour the airport - but easier to have a bit of cash on hand upon arrival rather than searching out an ATM under jet lag.
The reason getting a solid chunk out is problematic is simply that carrying tons of cash is risky due to theft, or just loss. And it takes up room. Are all your bags carry on? If you have to gate check your bag, will it have $500 in it (Not a good idea to gate check cash!!)?
Do the math between the exchange rate for cash vs the ATM fees…I'm not great at that. To me, it's close enough if your bank doesn't charge crazy fees. I get 300 - 500 Euros out at a time, because there are ATM fees and you don't want to pay them for a $20 withdrawal or whatever.
ATMs in Italy or anywhere else I've been are just like their US counterparts. They offer English on the home screen (push the British flag), usually let you choose between 20s or larger bills, and really are quite easy.