It depends on how much care you need.
If you are young, rugged, and hardy, travel Regionale. If you need more care, upgrade if you can.
On Regionale trains, I always have to stand with my luggage in the vestibules. Those trains are full of young agile travelers, students, soldiers, workers who can bounce up the stairs and toss their duffels up on the luggage racks and sit down at the same time.
I'm nearing 69, travel alone, and I'm always among the last on the train, along with other old folk who share the vestibule with me. It's tiring to stand and on a recent especially long Regionale train, every jerk threw my lower back out.
The pain was so bad I groaned all the way.
The train stop at Termini was staggered, giving us a one or two mile walk to the station. I was the last to make it to the station, I was so tired I could Not remember how to say or spell my hotel's street. I had written out the address but could Not remember where I put the piece of paper. It was late at night and I
Had put myself in danger.
Reserved second class is a tad better but only if I can reserve the solo end seats with floor space for my luggage. I am Not able to lift my bags onto the luggage racks, and I cannot always count on help being there all the time for me. Then there's the aggravation of other passengers in my seat. They don't have to get up. There's no one around to enforce my reservation. I'm on my own.
On First class there are a lot of old people there for the same reasons. There are professionals too. My seat is always available for me. There are "A" spaces in between seats for luggage storage. If my seat suite is empty I bring my luggage into my suite. If I need to use luggage racks overhead I can always count on a nice man to hoist my bags up and get them down.
The seats are larger and have tray tables for my laptop. Some cars have WiFi so I can send emails to hotels and my families and do Internet research. I can leave my seat and it is waiting for me when I return.
First class is more Fun, relaxing, and therapeutic. My body is intact and refreshed when I reach my destination, and I can take on the world again. So I always travel First class if available. There is time enough when I have to travel Regionale. So if I can give myself a First class break I take it.