Need help with itinerary

I would visit London on the end of the trip. It is easy to get from Heathrow to Oxford so that won't be an issue. But getting from Wales to Heathrow means either going all the way to London and then backtrack to Heathrow, or a change in Reading. And the closer you are staying to the airport on your last night, the less risk of something messing up your travel.

From Penzance in Cornwall to Cardiff is a 4 hours drive. It’s long, but not terrible. Depending on how you schedule that part of the trip the drive could be much shorter. From Tintern in Wales to Heathrow is only a 2.5 hours drive, so you could drive it as easily as taking the train. Also, since you’ll be over jet lag when you pick up the rental car, just pick it up at Heathrow. The Cotswolds, depending on where in that area you’re going, is as close as a couple hours drive. As the trip is a long way off, times, distances, and best mode of transportation will become clearer once you have more of an idea where you’re going and what you plan on seeing.

I took 3/4 of this trip in 2019. We visited London for 4 nights, picked up a car at Heathrow, traveled to the Cotswolds for 4 nights, then went to Cornwall for 4 nights, then drove back to Heathrow. Cotswolds to Cornwall was the longest drive. We stayed in the Northern Cotswolds (Snowshill) and it was slow getting to the main multi lane high ways.

Cornwall is a bit of a haul to get there and only worth it if you can spend more than 2 nights. (IMHO). You don't say what you are planning on doing for this trip. We allowed time to do an all day walk in the Cotswold, and an all day walk in Cornwall. We had 17 nights, and it would not have worked to fit Wales in too.

Picking up a car at Heathrow is easy. You are on a freeway from the get go. I think it is a better option than Oxford where you will immediately be driving on smaller roads through smaller towns. My husband appreciated having time to adjust to the car and re-adjust to shifting with right hand while driving on the left side of the road for a couple of hours before tackling towns.

You have received some good advice about laying out the trip. I would just add that if you do drop the car in Wales, there will probably be a drop off fee. We picked up a car in Wales and dropped it at Heathrow in 2002 and had to pay one. (I don't have the paper work anymore) In 2014, we paid $50 to pick up at Heathrow and drop off in Scotland. For us, it was worth it because it allowed an additional full day in Edinburgh that we would have had to spend driving back to Heathrow.

We did four week driving around the English and Welsh countryside in 2017. Love it.
28 days in Britain and Celebrity Eclipse home
https://www.cruisecritic.com/memberreviews/memberreview.cfm?EntryID=599139

My detailed review provides places to stay, tours to take, places to see in Bath, the Cotswolds and South Wales.

We haven't been to Cornwall yet, but expect you could easily spend a week in Cornwall. We planned to stay in Truro in 2020 but had to cancel due to COVID.

If you stay in the Cotswolds with a car, I recommend The Volunteer Inn at Chipping Campden. It is a small BnB and has the best pub in town as well as a great Indian restaurant. Its rates are good.

Don't miss Stratford Upon Avon, especially if you like Shakespeare.

When traveling into S. Wales, take in some of the castles (there are hundreds of castles in Wales) . My review explains what we visited. The Museum of Welsh Live just west of Cardiff is worth a visit. Also, we loved Tenby and St. Davids.

Cornwall is a must see especially the very west coast. Our favourites were st Ives, Zennor, Botallack, Godrevy lighthouse to see the seals, fisherman’s creek, porthcurno beach. Paradise.