A couple of years ago I flew into Guadalajara for the first time. Now, I am doing it almost 60% of the time. GDL is an easy airport to use. It has better, less expensive, and more frequent flights than Manzanillo. We can fly into GDL and rent a car for about the same cost as a flight only to Manzanillo. It is an easy 4 hour drive from the GDL airport to Manzanillo -- most of it on 4 lane divided toll highway. The tolls for a one way trip total 320 pesos for a car and passengers.
The GDL airport is at the end of a large cul-de-sac. As you exit the airport terminal there is a car parkade directly in front of you.. Bear left and about 150 yards away are 6-7 car rental yards. I just walk to National Car rental and pick a car. (Daily rate +$14/day liability insurance+optional insurance+significant taxes= approx. $300 week).
From the airport it is approx. 1 km then head north (left), drive 7 km then head west (left) on Anilo Periferico Sur (hwy). Drive 3 km and see a City Junior Suites hotel on your right -- like a Holiday Inn Express (good place to stay $60 night). Drive another 9 km and see Pemex station on right with Holiday Inn Express behind it (not good value for money $90 night).
Drive 1 km and take interchange south (left) --to Colima - it is multiple Hwys at this point -Hwy 540 /15 / 80. From there it is an easy 3 hour drive through interesting ranchland, green houses, dried lakebeds, some scenic mountains, and small towns. Lots of Oxxo stores and Pemex stations beside the highway.