We have very recently returned from far west of Chania. We hired a car via Alianthos Car Hire from Chania airport (to pick up and drop off), cash on delivery at the airport. The price was good, the car like new (although it wasn't the model we were expecting, but probably better in the end fuel-wise). They meet you after arrival, holding a sign up and you sign the paperwork there and then and check the car over (return with the tank half full). They have a desk at the airport and were responsive to our enquiries. The family company has been going for around 30 years and has a number of outlets on the island. They have as near comprehensive insurance as we could find
http://www.alianthos-group.com/en_services.html

Reason we picked up from the airport is that we were flight only and taxis aren't cheap for a transfer of any distance, and then we could take our time getting to and from the airport as well as getting around the north/west of the island. Petrol was more expensive than UK., but our car (some sort of eco Micra was extremely good on fuel). Our return to the airport was nice and relaxed as we stopped for lunch and shopping at our leisure on the way. How else can you do that?
As for driving from the airport. We bought a Crete Road Editions map before going (a lot of the tourist maps are quite inaccurate) and that led us to avoid Chania Town and head out Souda way to get onto the E65 west (no built-up town to drive through). Be aware that the hard shoulder where there are solid white lines is used as a kind of slow lane, and you're expected to drive in (or semi in) it to allow others to pass. Watch out for the slips on and off where there aren't solid white lines and move over into the lane proper for a short distance.

Thanks very much for that Phoebe.

Hi Tosca,
You're going to the most beautiful part of the island. I generally agree with Phoebe. Try to avoid taxis at the airport. Car hire is a bit more expensive at the airport but not so bad if you can strike a good deal in advance. For reference current non-airport rates are:
Class A (smallest): 26 euros per day plus 0.14 per km or 78 euros for 3 days with unlimited mileage. 132 for 7 days.
Class D (medium) is 37 euros per day plus 0.20 per km, 7 days 250 euros

It's not too hard to get to the motorway, just follow signs for Kissamos which is where the motorway heads west from Chania. The motorway is not crowded, especially in May......and the flowers will be fabulous, especially in Samaria.