Least stressful town to rent a car in Ireland?

If you return to the airport and pick it up there, you're not going terribly far in the "wrong" direction. Or you can take a direct train to Cork in only 2.5 hours or to Kilkenny in 1.5 hours. Enterprise is located at Kilkenny train station but Europcar is futher away, per Google Maps.

I would pick it up at the Dublin airport. You are pretty out of town and getting on a major highway which is not a bad way to start driving on the 'wrong' side.

Second vote for Dublin airport.

After a few days in Dublin, I took a bus back to the airport where I picked up a rental car and then drove to Glendalough and Kilkenny where I spent the night. Getting out and on the main highway was easy with no city traffic to deal with. It was easy returning the car there as well. I used my phone's Google GPS for directions.

Thanks for the replies, and I'm certainly interested in more opinions, if they're out there. I also asked this question on a TripAdviser forum, and while one person advocated City Centre because the traffic was slower and often one-way, the consensus there seemed also to be the airport.

Many on this forum recommend Dan Dooley for car rentals in Ireland. Their rates are very competitive, and an explanation of the insurance cover is clearly explained - not exactly the norm when renting from some of the other companies I'm afraid. They have pickup points in Dublin center, Dublin airport, Shannon airport, and elsewhere around the country.
Here's their website: https://www.dan-dooley.ie/
Might want to take a look and see if any of their pickup points appeals to you, remembering that you could also drop the car at one of his satellite locations and then just train back in to Dublin for your last night...thus avoiding the hassle of an airport drop-off.
Though I agree that driving in Dublin city isn't a good idea, especially for your first adventure driving on the left, starting your journey from the airport is actually a pretty good introduction (in my opinion) since you'll be starting on Motorways and some of the "N" roads to help you get used to the sight picture of driving on the left, road signage, etc. before you try to tackle some of the more rural roads in the countryside, which is where the adventure really begins.
There have been many discussion threads here about driving in Ireland in general. Might be helpful to you to do a search of the website to read some past advice and commentary.
Safe Travels.

Thank you, Robert. I had been seeing generally good reviews of Dan Dooley, but was very put off when I found that the price I was quoted online was 200 Euros higher if I put myself in as the primary renter (I'm 60) than if I put my daughter in, who is 34. Hertz, for example, merely ascertains that you are over 25. If my daughter has a credit card with CDW that covers Ireland, we can make her the primary renter--I haven't asked her yet--but I do have that coverage, so I expect to be the primary renter, and don't feel disposed to pay far more for being an older driver, when I have a spotless driving record....

I will definitely explore the threads here for useful information--thanks again.

Be especially careful when sorting out the matter of car insurance in Ireland. Most credit cards won't cover you there, and many contributors here have reported some very bad experiences in trying to settle claims with those that claim that they do.
The whole matter is so fraught with confusion (and risk) that we, along with many others, simply opt to take the cover offered by the rental agency ... just for the peace of mind involved.

I've been researching this, and am very confident that my Chase cards (when used to pay for the rental, with me as primary renter, when the rental is <31 days) cover everything the agency CDW,SCDW, and T&G do. I've confirmed this over the phone, and with my copy of the Card Benefits statement. But you're right--many companies/cards do not cover Ireland.

Only disadvantage is that the agency will most likely put a large hold on my card, and if they charged me directly for any damage, I would have to be reimbursed by Chase. However, I am okay with the hold.

"Only disadvantage is that the agency will most likely put a large hold on my card, and if they charged me directly for any damage, I would have to be reimbursed by Chase. However, I am okay with the hold."
Yes, that's the tradeoff.
Sounds like you've already researched this and are well prepared for your trip.
Only other bit of advice I'd offer if this is your first trip to Ireland...and maybe your first time driving on the left too: we've benefited greatly by previewing our daily driving routes using the street map feature on Google Maps. It helps us to have seen parts of the route, along with intersections, roundabouts, signage, etc. before approaching them at speed. Might be useful to you too.

That's great advice. My daughter and I will probably be sharing the driving and navigating duties, but if she proves more at ease behind the wheel, it will be mostly her! It will actually be my fourth trip to Ireland, but the first in almost 40 years. Earlier trips were when I was a teenager, and my dad did all the driving...

Something I haven't looked for yet on a forum--should I get the International driving license, or will I be fine in Ireland with just my valid state license?

That's great advice. My daughter and I will probably be sharing the driving and navigating duties, but if she proves more at ease behind the wheel, it will be mostly her! It will actually be my fourth trip to Ireland, but the first in almost 40 years. Earlier trips were when I was a teenager, and my dad did all the driving...

Something I haven't looked for yet on a forum--should I get the International driving license, or will I be fine in Ireland with just my valid state license?

I've never bothered with an International Driving Permit (IDP) for Ireland, and I don't think one is required for either the Republic or NI, but you should confirm that with a definitive source...maybe a Google search would answer the question.

Another thought: you should confirm with whoever you book the car with that they accept the Chase CC coverage, just to avoid any unpleasant surprises as you're standing at the rental car desk.

You're right; I have even read that people can confirm this with the rental agency at the time of booking, and still be told at the actual desk that it won't be accepted. I plan to book directly with the car rental company, rather than go through a third-party agency, to minimize that chance, and if it happened anyway, I would just go somewhere else.

An international drivers permit is simply used in countries that do not have English as their language. Not at all necessary with Ireland. Good advice about the car insurance.