1 Do you really need a car? If you prefer a multi location holiday having a car will give you more flexibility. If your accommodation is not close to your arrival airport it may be a bonus to have the car for the transfer. If you are staying a more rural location it may be useful to have your own transport.
2 Are you a fairly confident driver? Are going to a nervous wreck, worrying about each days drive? For example in Italy you will probably be honked at quite a bit, can you just shrug it off? I don't find that driving on the right hand side of the road is an issue, especially when you are in a left hand drive car.
3 Make sure that you have comprehensive insurance cover. Many rental companies so - called inclusive cover can often leave you with an excess of several hundred euros. As I hire a car in Europe several times a year I purchased an annual insurance cover for around £50. If you don't hire a car frequently then you can pay an additional amount per day, around £2 sterling, with Holiday Autos. with Auto Europe some prices are quoted with a excess refund included. Check if there is an extra charge for additional drivers.
4 Check if there is parking available at your accommodation. Some hotels charge for this. Will there be on street parking fairly close to your accommodation?
5 Invest a decent road map for the area(s) you are visiting and plan your routes in advance. Make a note of the road numbers and the towns along the way to your destination.
6 Be alert for road signs. I find that the roads signs are not as large and clear and don't give as much advance warning of junctions as in the UK.
7 Try to avoid city centres. Park in the outskirts and walk or get a bus in to the centre.