OK, if he has driven there before, he will probably be OK, even if he's a little "rusty". Definitely confirm that your reservation is for an automatic. It's one less thing to think about, especially since he would be shifting with his left hand. I can drive stick, and have done it on the continent, but in the UK I insist on an automatic. A compact will be ideal.
A larger car can be "interesting" on some of the tighter, more rural roadways! On my last trip to England I had ordered a C-class Mercedes, but they were out of them and I was upgraded to an E-class. It was a beautiful car and fabulous on the motorways, but a bit more challenging on smaller roads, expecially on one rural road near Bath on the very first day, before I had fully gotten to know the car. There was a stone wall on one side and a large lorry coming at me on the other side! It was tight but fine, but a little nerve-wracking. And I'm a confident driver!!
Here is a link to the UK Government site that has a download for the various traffic signs. Most of them are pretty straight forward if you've driven internationally recently, but it's a good review or reminder. And keep an eye out for warning signs for speed cameras.
Traffic signs used, including signs giving orders, warning signs, direction signs, information signs and road works signs.
www.gov.uk
I think Enterprise might be simpler to use. Waverly Station is right in the heart of the city, and therefore more congested. It has been a while since I was last in Edinburgh, but here is a route suggestion that should avoid the worst of the central congestion in Edinburgh. I haven't used it myself, so you might want to run it by someone at the hotel or check it out on Google streetview.
The street outside your hotel, that Annandale also runs into, is the A900, you can take it from the rental place to your hotel and then follow the A900 to York Place (by St. Paul's and St. George's Church). Turn left onto York Place, which becomes Queen Street. It is a bit more residential and hopefully less busy. You can stay on that street to the very end at the Ainslie Place roundabout. Stay left onto Great Stuart Street and Randolph Crescent and it will take you to the A90 (Queensferry St.). Turn right and follow the A90 to the M90 and that will take you to the bridge over the Firth of Forth. You are now headed north on the M90 past Dunfermline and Perth towards the highlands.
Good luck and have fun. Scotland is beautiful.