quaint villages along lake district to wales route

I don’t know what “quaint” means but Ludlow is a good place to visit. Or Ironbridge Gorge.

I'm assuming your route as far as Shrewsbury is M6- M56-M53-A55-A483- A5.

Admittedly I start from 30 minutes beyond Keswick but I wouldn't want to go from Keswick to a bit south of Chester without a brief intermediate stop somewhere.

Rather than going straight down the M6 from the Lake District I would do A591/A6 and have a breakfast stop at the legendary Sue's Cumbria Snack Bar in Milnthorpe Square. That should be about an hour into the journey. Then pick up the M6 at Pine Lakes (Carnforth), junction 35a.
Ideally I would divert via Arnside, Silverdale and Warton between Milnthorpe and Carnforth

Then first stop in Wales I would make Chirk/Pontcysyllte Aqueduct, although Chirk also has it's own impressive Aqueduct.

For the second stop everyone on here seems to stop at Ludlow- I would suggest Leominster instead as your mid afternoon stop.

It’s a pity that you are doing this as one long day drive as there are many places to see along this route. (If I was driving from the Lake District to Newport, I would use the M6 to Birmingham and then the M5 south to come off N of Tewkesbury and use the M50 > A40 > A449 expressway to Newport as it is the faster route).

Anyway, coming down the route near the Welsh border, as already mentioned above, divert off A483 to see the wonder of the Victorian age:>https://www.pontcysyllte-aqueduct.co.uk

Stokesay Castle - just N of Ludlow on the A49 is worth a stop. Also take a look at Ludlow - best of view of castle is from W side of river.

Leominster is OK but I would not rave about the place.

Hereford is worth a stop but does suffer from traffic jams as several main roads converge on this small city.

Going S from Hereford, you have a choice of several routes. I would favour the A465 going SW towards Abergavenny (which you by-pass). Then take A40 going east and be sure to stop at Raglan Castle - which will be a sharp turn off to your left.

On exiting Raglan Castle - turn left and follow signs for A449 which will be an expressway to Newport. DO NOT use the A4043 from Abergavenny to Newport - congested with loads of roundabouts. Why Newport?

James has already mentioned Stokesay Castle which is definitely worth a stop - and don't miss the church next to it

You are spoilt for choice for 'quaint' villages around there - Bishop's Castle, Clun, Lydbury North... A bit further are Knighton, Leintwardine, Leominster, Kington - would all fit the bill....

Thanks so much to everyone for your helpful suggestions! We are American, and as to why Newport... my daughter just married a lovely man from Wales last July and we are headed to Newport to spend a few days with Thomas's parents. This trip through England and Wales is a gift from our daughter and son-in-law. Point of interest, their reception was at our smaller, Pennsylvania version of Stokesay Castle! You can Google it near Reading, Pennsylvania. So, it might be fun to see the original. Many thanks again!

Well, that does rather seal where your second stop is then- Stokesay Castle. Probably not too many people over here know of the 'copy' in the US.
And yes says why you should come down through the Borderlands rather than the motorway via Birmingham route.

I expect they will have plenty of day trips lined for you in SE Wales and nearby England.

You say “skirting Chester”. Yes, you can skirt Chester but this city is well worth seeing.https://visitcheshire.com/locations/chester

If it is just a quick stop for something to eat, there are a couple of small towns just off the M6 in Cheshire. Lymm and Knutsford. Both quite "quaint", with places to eat, places to walk to stretch your legs before resuming your journey.
Personally, I would favour Lymm. Among others, the Golden Fleece pub does food and has a nice beer garden overlooking a canal. You could have a look at the lower dam and it's only 10 minutes to the upper dam.
Knutsford has plenty of restaurants, wine bars, coffee shops etc.
Chester is a larger place and very nice, but not really car friendly. By the time you have driven into the centre, parked up and walked to the shopping area, you will have eaten into your journey time.

When you’re in Newport you should try to visit nearby Caerleon. You can see the ruins of a Roman amphitheatre and army barracks all for free with barely any people around, and for a charge can visit the Roman Army Museum and Roman baths. It’s a great place.