Which hotel of these three is best for safety and location in Paris?

Not la Defense -- the other. two are at least in Paris. Safety is not an issue.

I would care about metro access primarily, and the 3rd hotel seems to have the closest station. I can't speak to safety for each location, but if I had to choose, I would go with #3.

As for #2, it is right next to the train yard for Gare de Lyon...not very pleasant looking on a map.

Overall I am not a big fan of the La Defense area. I would not want to return to that primarily office building / commercial business area at night, for instance. I don't even like being over there during broad daylight, but YMMV.

Also I would read the reviews for each hotel carefully and look for hints of security concerns in the comments.

Generator is a hostel. For a 22-year-old on a short stay I would think the hostel environment would be ideal if they can get a private room (if that matters to them). I have not stayed in that Generator, but stayed in another of the same chain and found it to be great. I wanted to book this very hostel in Paris for the upcoming trip, but it was booked for my nights. I wouldn't have any qualms about this location.

My first choice would be the Hotel Claret Bercy because it is right next to the Gare de Lyon, and a block from the Seine River, and has the most metro and bus lines connecting there. The area is filled with restaurants. It's the most central and just down the block from a Marriott and Citizen M. But my choice and reasons for the choice may not be theirs.

Stay City Aparthotels La Defense isn't really in La Defense but in a neighboring suburb Courbevoiem, just outside Paris. It's still too far. BTW, La Defense is not terribly safe at night because it is so deserted.

Generator Paris does have one Metro line, the 2, in the Place Colonel Fabien but it is further from the center compared to the Gare de Lyon. I haven't been there since the Place was redesigned, but the Place du Colonel Fabien is well-known because it's where the large, architecturally designed headquarters of the French Communist Party is located. The Party played a very important role in the French underground, liberation, and politics until the 1980s. The CGT union leading the recent strikes is affiliated with the PC (Partie Communiste). Plenty of guards around. It's just a bit out-of-the way but more a local neighborhood rather than one with a lot of tourists, restaurants, or metro lines.

Hands down #3, especially for a 22 y.o. Right next to some of the arguably coolest/hippest parts of the city (Place ste Marthe, Canal St Martin...).
The area around #2 is a snooze, hemmed in between the railroad tracks, the Ministry of Finance, and a large concert/sports venue.
And #1 is not in Paris proper.

Thank you all so much! I have passed all of your replies along to my niece. She and I were both leaning towards Generator Paris, so it is nice to have it confirmed that it is in a safe area and a good spot for young people! She and I both thank you very much!!

La Defense is a business district and safe. Also Bercy is pretty safe. Generators are always in more 'vibrant' hoods so would not recommend.

The Generators I stayed in in Stockholm and Copenhagen weren't in "vibrant in quotes" neighborhoods. Stockholm neighborhood was rather staid, and Copenhagen was simply central, with good access to lots of sites, public transport, shoping and restaurants. Well, come to think of it, that does sound vibrant.

La Défense is safe during the day but after offices close there have been some problems.