The "direct route" which I believe you refer to is all gravel, is at high altitude (over 4000m most if not all the way), and will probably take a couple days if you don't run into snow or other bad weather. Not much along the route for travelers.
Hopefully you aren't prone to altitude sickness. I talked with a 4-wheel adventure travel outfitter - they had to stop doing the route because too many clients got sick on the ride just sitting in the cab for that long.
blazeafar is correct about the road to Juliaca as being good. Actually, he left out the part that its paved the entire way - major truck route. You could do Arequipa to Cusco in one long, hard day, but its doable (start early).
My Rough Guide map was very outdated on the roads in this area. The road to take from Arequipa is north out of town, on the way to Colca (the canyon). There will be a split about 90km up the road - right to Juliaca, left to head north to Canyon de Colca (paved) but about 30 km up the road is the split once again to head to Cusco (gravel at that point).
Buen suerte!
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quastdog
Chiang Mai, Thailand
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