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