I've driven a fair amount in France, Switzerland, Austria - mainly in the alps - and Greece (hideous roads) but always in lefthand drive, manual hire cars. I was really very nervous the first time, dealing with both a left-handed car and driving on the 'wrong' side of the road but got used to it surprisingly quickly. I think being in the lefthand drive car makes the whole experience feel much more natural but the obvious left hand turns at junctions, coming off motorways or dual carriageways and roundabouts, demands a lot of your attention (As already mentioned.) especially when you're tired.
Hope you have a great trip and get the taste to do a longer one next year! I'd love to do a long continental road trip, I think the whole airport experience ruins both ends of a holiday (especially now we have a toddler in tow). And you get to experience the country you're traveling through far more than at 30,000 feet!