If you were to pick up a hire car in Holyhead, you would certainly see some fine Welsh scenery as you drove south eastwards across the country. The A5 is a fast dual highway that would get you swiftly to the mainland. You would then head for Caernarfon - which has a fantastic castle. Then on to Porthmadog - which takes me about 30 minutes on a good run. Leaving Porthmadog - which has a by-pass, you head for Dolgellau and then just keep following the A470 all the way to Cardiff via Builth Wells. Porthmadog to Cardiff is 150 miles and it takes me 3 hours 30 minutes on a clear run with no stops. So, the leg from Holyhead to Porthmadog would take about another hours and a half. The trouble with all this is that it is solid driving and you are shooting though all of the things that you should be seeing in Wales. It is not the best plan! Far better, in my opinion, to hire the car in Holyhead and drive to say Caernarfon or Porthmadog and use that as a base for 3 nights in order to explore NW Wales. Then make your way south.
Don’t bother with the car hire to Aberystwyth idea. You might as well keep the car for the entire trip. Alternatively, direct trains run every other hour from Holyhead to Cardiff via Chester. These trains are air conditioned Class 175 units operated by Arrival Trains Wales. Schedules & fares (cheaper to advance book specific trains about 11 weeks out) > www.nationalrail.co.uk
Please note that in the autumn & spring, that ATW often have special deals for the over 55’s. Currently, this means that you could get from Holyhead to Cardiff for only £24. Google 'Arriva Trains Wales Club55' if appropriate.
Here again, you are passing through places of interest. The first of these is Conwy - which has a wonderful castle - but you would not realise that you are actually passing beneath its walls. The next place worth a visit is Chester. The train then heads south roughly following the border and the next place worth an hour or two is Shrewsbury. Another 45 minutes or so south is Ludlow - which has some fine olde buildings. By pre-purchasing a through ticket for specific train, you are not allowed to hop off and catch a later service. (Trains are at hourly interviews roughly linking these places). So, you could of course by tickets for each leg or check if you can purchase an ‘Anytime ticket’ and that this would permit hop offs at places of interest.
Another way of doing the journey using public transport is to go by train from Holyhead to Bangor. Then bus to Caernarfon - see castle. Then take Welsh Highland Narrow Gauge Steam Railway through the Snowdonia National Park to Porthmadog (stay 2 nights?).
Visit Portmeirion on day in Porthmadog or ride the Ffestiniog Railway. Then, leave Porthmadog for Cardiff by ‘normal’ train - which is slow going as it hugs the beautiful Cambrian Coast before turning inland to head east to Shrewsbury where you can change for a Cardiff train. (I would have a walk around Shrewsbury first).
Google the places mentioned for more info.