I think Penzance is a great place to stay. Not only is it a good base for transport to other places in that part of Cornwall, it is a nice place in itself. If you like to walk, you could actually walk to and/or from Mousehole.
One of the times when I was down there, they were doing track work, and on my way back to London we were bused from Penzance to, I think, St. Austell, where we met the train. It was very well organized, no problems.
The train ride from Paddington to Penzance takes you through some lovely country. Even if you have to be bused part of the way, and I hope that doesn't happen, it is still a trip worth looking forward to.