Mid-September trip to Wales

I would not worry about the distance on day 1. It should be about 1.5 to 2 hours of highway driving along the M56, around Chester and the A55 to Conwy. You said our trip so I assume that there are atleast 2 of you. A navigator can be extremely useful and I would get a detailed map as well as GPS. I normally find the adrenalin kicks in on the first day of vacation but if you are feeling jet lag, just take a break and get some fresh air.
Most tours and guidebooks focus on the northwest of Wales because it has lots to see in a small area - 5 castles, Bodnant Gardens, Great mountain and coastal walks, and wonderful small towns. I would probably spend half your 6 days there.
Heading south you have few choices and variations on each -
1. A470 ( or A496 coastal route which passes Harlech Castle ), then A 487. To Aberystwyth the road goes mainly through forests and is hilly. After it becomes more rolling farmland and closer to the sea. I would continue as far as St David's as the cathedral is spectacular and uncrowded. The direct road back to Cardiff becomes 4 lanes around StClears. If you have the time, I would follow the A 40 to Brecon,then down one of the valleys to Cardiff.
2. You could cut off some time by taking the A 470 at Dolgellau and going straight to Brecon. There are some interesting small market towns along the way.
3. You could als take the A 5 to Shrewsbury then follow the Welsh border down to Chepstow and along to Cardiff. This route can take you through larger towns.
I am sure a guide book for Wales - lonely planet, Michelin, or fough guide would give you all the information you need.
Enjoy your trip!

If you are landing in Manchester I would recommend staying overnight in Chester. It is a town that was first a Roman fort for the XX Legion. It has a wall that you can walk around the City...to get your land legs back. A historic shopping street called the Rows. Plenty of places to stay and eat. Conwy is a easy drive in the morning. It is a very small town. The Castle will take 1 hr. to visit. Be sure to buy a Castle pass. You can then visit Beaumaris on the sea coast which is only 24 miles away. I would also recommend spending a night in Betws-y-coed which is on a rushing river that looks like a Fairy Glen. September weather is always a surprise, but can be hot and or wet. Watch out for sheep on the curvy roads in Snowdonia. It is easy to visit most of Edward's Castle...just plan ahead so you don't have to back track too much. Look on Google Earth for some idea of the topography and where the highways can lead you. Bon Voyage.

Thank you for your ideas and help! I appreciate it!

Planning similar trip (landing in Manchester, spending three days in north wales), only in mid August.
Does anyone have specific hotels/lodging they can recommend in Conwy and Betws-y-coed?

Definitely stop in Chester and perhaps stay overnight. Then head to Conwy (next day?) with perhaps a detour to see the Victorian seaside resort of Llandudno. (You may like to book a night in this area as you would also need about 2 hours to see Bodnant Gardens). On leaving this area, I would head south on the A470 to Betws-Y-Coed. (Also a possibility for a night or 2 - if you do not stay in the Llandudno/Conwy area).

Be sure to drive through the mountainous area to the SW via the A5 to Capel Curig and then A4086 - perhaps through the Llanberis Pass to Llanberis - for the Snowdon Mountain Railway. (You could continue on to Caernarfon to see the Castle). A498 via Beddgelert is also very scenic. (You could continue through the Aberglaslyn Pass to Porthmadog and then visit Portmeirion).

When you start heading off to south Wales -I would definitely take the A496 coast road via Harlech (Castle at top of hill in village) and Barmouth.

From Dolgellau (worth a look to see the house made of blocks of stone), you could head directly south on the A470 through the middle of Wales - with perhaps an overnight in the Brecon area. (Porthmadog to Cardiff via the A470 direct route is 150 miles and I have done it in 3hours 30 minutes driving time). Anyway, you are probably heading for SW Wales so will use the A487 via Aberystwyth - worth a look or overnight - just check that hotel has parking. Continue down the coast and be sure to stop at Aberaeron and I would also take a detour in New Quay.

Near Newport (between Cardigan & Fishguard), consider a detour down some country lanes to see the Pentre-Ifan Burial Chamber.
You could continue to St.David’s. If you want to shorten your journey, this can be done from New Quay to Carmarthen but if doing so from Cardigan, you could go via the A484 to Carmarthen - or head south on A478 to Tenby = lovely walled town with harbour. (Stay 2 nights)? Lovely coast west of Tenby - especially Stackpole > Barafundle Bay and Bosherston pools.

Tenby to Cardiff is 96 miles and takes about 1 hour 45 minutes non stop driving via M4. However, as previously mentioned, a longer more scenic route can be had by going from Carmarthen east along the Towy valley to Llandeilo and continue to Llandovery (or short cut direct to Trecastle via back roads). At Sennybridge, take A4215 SE to join A470 for Cardiff via the Brecon Beacons.

For lodging in Conwy, I stayed at the Castlebank Hotel last September and really enjoyed the accommodations and the hosts--Jo is Welsh and Henrique is Portuguese.

We stayed at Maes-y-Garth in Betws-y-Coed and it was wonderful. While a B&B, it was purpose-built and the rooms are comparable to a good hotel. It is in a quiet location, about a ten minute walk from the town centre and has off-road parking. It is on the side of the Convy Valley with spectacular views from the porch. Check it out at booking.com.
We really enjoyed our time in Betws-y-Coed and hope you have a great trip.

What's the approximate driving time from Betws-y-coed and heathrow, on a Sunday?

Right now - on a Friday = 220 miles in 4 hours. (I would generally advise that people actually use such a trip to see places en-route rather than just get from A to B).
http://www.theaa.com/route-planner/index.jsp#fromNode=0%7CBetws-y-Coed%7C%7C-3.801035%7C53.093086%7CtoNode=0%7CHeathrow%20Airport%20(LHR),%20Longford,%20Hounslow%20TW6,%20UK%7C%7C-0.454295%7C51.470022

Manchester to Conwy- probably will take 2.5 hours--- but its not something I would do jet lagged after a 13 or 15 hour flight especially if you have not ever driven in the UK before..its a bit weird when you first begin to drive their roads since they feel 'backwards' and there are a ton of roundabouts. I'd really stay in Manchester one day to recover.

I think its feasible to follow your driving route going around the coast, but its very ambitious and will not allot much time to get out and visit things. Places in England - particularly Wales can take hours of your time, and they should. Conwy Castle takes about one hour to see, but if you plan on visiting Carnaefaron (sp?) that is a good 3 hour visit and much nicer than Conwy (imo). Beaumaris takes around an hour or so. But you also have to get there, park your car, etc. Bodnant garden could take someone 3 hours easily if they want to fully explore the place- after you already arrive there...and you also need to factor in some time to eat...

Driving around snowdonia is particularly slow going (slowdonia?) the roads are windy, two laners with lorries/trucks all over the place that can crawl you down to a 30mph slug-pace. In one instance my friend and I were driving around and saw a truck actually stuck on a bridge that was frequently used... sheep are also everywhere so you have to watch out for roaming rams and ewes that have escaped from their pens.

You might get more out of your trip if you spend 3 days in Bangor or Conwy and use it as a base to visit northern Snowdonia, then drove the fastest route to Cardiff (if you want to see S.Wales). A drive from n.slowdonia will take you a good 4 hours.

I'd really book your places far in advance (six months out), or you may not get them, they tend to book up quickly.

If it's not to late, try to stay at the Gwynfryn (gotta love the language) B & B in Conwy. A good side trip from there is an old slate mine in Blaenau Ffestiniog. You can get there by train from Conwy or, if you are a bit adventerous, you can drive there. I did. Not for the faint of heart!

We are staying there! Thanks!

I just wanted to say thank you for all of you who contributed to our trip with your advice. My daughter and I enjoyed Wales tremendously. Thanks, James, for your tip: we loved Tenby. We started at Conwy, loved the drive through Snowdonia, hiking, and green on green fields all the way south. We enjoyed the mine tour, castle tours, and the lovely Plas Mawr in Conwy. We just got home from a month in Europe: the best fish and chips we had were in Conwy. The only part we could have missed was the terrible traffic on a Friday going north from BATH TO CONWY. We just could have planned our travel day better. Thanks to all.

Many thanks Dee for coming back after your trip and it is good to know that advice given proved useful. Unfortunately, many people who put questions on the forum do not always come back to acknowledge that they have even been back.

Fridays are often the worst day for traffic congestion.

I have never heard an American accent on visits to Tenby. It appears to be completely unknown to north Americans. Of course, part of the reason is that it is so far from London. Cornwall often gets a mention on these forums but practically never Pembrokeshire = SW Wales.