Guayaquil is a better bet for departure and the drive from Cuenca is spectacular.
Round trip from Guayaquil to Arequipa presently costs $321 on LAN. Keep in mind that prices fluctuate and will go up as you get closer to your travel date because the cheaper seats get used first.
Figure 2 or 3 hours drive from Cuenca to Guayaquil. For your trip, Guayaquil-Lima-Arequipa is the route to take. You can save about $60 if you take an extra 7 hour drive from Guayaquil to Piura but I think you would not have much savings left when you factor transport and hotel which may be needed between.
If you do it all on a single airline, there is less hassle but you have fewer choices. You may look at doing the Lima-Arequipa way on Peruvian Airlines but it looks like doing both with LAN is cheaper at this time.
The road from Lima to Arequipa has some sites to keep you busy but it is desolated and long. Figure around 12 hours excluding stops. The driving conditions are very good though along the entire Peru coast, although I have only done it both ways twice and prefer to fly one way. To get variety, once I did the northern coast (Lima-Mancora) and came back through the cordilera but that is considerably slower and with very difficult driving conditions for large segments.
Definitely Guayaquil to Lima should be a flight if you are not interested in the area. There are some gems of cultural interest, colonial towns but lots of empty space in between.
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