Flying to/from regional airports in Europe

There won't be any problem. If you can't read French then there will be instructions in English or pictures. It will be a less stressful experience than starting your journey at a major airport but the process will be the same.

Go to their respective websites to find out more.

If this is one ticket from Nice to the US then you check your bags in Nice and collect again when you arrive in the US. SImple.

I'm not sure how you define regional airport, but Nice and especially Barcelona are not small airports. Barcelona handles over 50 million passengers per year which made it the 7th largest airport in Europe in 2018. Bigger than Munich and Gatwick, and only a few million passengers less than San Fransisco.

I have flown out of all of those airports. They operate like all others, so you will just be using common sense like people that understand a routine but are unable to read in any language. Arrive at the airport 2 hours before the flight so you don't have to rush that is when people have problems.
Most airline customer service people in checkin and screening speak enough airport operation English so there is no language barrier.
And if you have one ticket your bags will check all the way through from Nice.

What ramblin' on said. Airport procedures are similar the world over. If you can't read French or Spanish, and you don't see English, then the pictograms should suffice 9 times out of 10. Worse comes to worst- use Google translate.

Efficiency at security, Passport Control, baggage pick up, is as variable as any other airport. Sometimes it's excellent, sometimes it sucks. Don't overthink it, and just allow plenty of time ( 3 hours for your return flight). Frankly, I'd rather travel through a smaller airport than a concrete jungle like OHare, JFK, or CDG any day. But I would hardly categorize Barcelona as a small regional airport.

I wonder if you mean to ask about the secondary airports used by some "bargain air carriers", like Ryanair's selling tickets to Brussels but delivering you to Charleroi? Just like a discount transatlantic from Hartford, CT or Westchester County, NY instead of NYC or Boston, it can cost a lot more, take a lot longer, and be less frequent intervals to get back to civilization!

Yeah and Nice is not a small regional airport. It has 2 terminals and flights to and from the Middle East and North America

An airport is an airport. I have flown out of big and small airports both in Europe and the U.S. and found only one--Reykjavik City (not Keflavik)--to be inefficient. And that wasn't the airport's fault as the airline was running the terminal.

Since English is the most common second language in the world, and taught in schools to many Europeans, almost every airport in Europe has signs in English. (There might be some small ones in far eastern Europe that don't but they probably do as well.)

If you are flying on one ticket, then your bag should be checked through to your first port of entry into the United States. Wherever you enter the U.S. is where you will have to collect your bag for U.S. Customs (if flying from a pre-clearance airport you do that before leaving for the U.S. but CDG is not one of them.)

If you are flying on two separate tickets, you may have to collect your bag at CDG and re check in.

At CDG, you will have to go through exit passport control to get your passport stamped.

And as stated earlier, Nice is not a "small" airport. Unless you compare everything to O'hare.

Thanks to all. I figured procedures would be similar all over, but it's nice to get some verification. And yes, O'Hare is my closest airport, so I tend to compare to that. From the responses, it appears I have been underestimating the size of some of the airports in Europe. I definitely don't want to be the know-it-all American tourist so my apologies to cities all over Europe.

I had a couple of decisions to make between a 9 hour train + connection time vs. 90 minute flight for essentially the same price.
Looks like the flights may be a quite reasonable option.

Thanks again to all.

To answer your original question, most larger airports have multilingual signs so you shouldn't worry. The signs at Nice are bilingual (French/English) and at Barcelona they are trilingual (Catalan/Spanish/English).

Many smaller airports only have signs in the local language, but those are usually very small airports where there is almost no chance to make mistakes.