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Visiting mountain towns and Lake Titicaca can bring on soroche (altitude sickness). Temporary cures include mate de coca (coca tea) and chancaca (crystallized pure cane sugar). Drink lots of bottled water and forgo alcohol, coffee, and heavy meals.
Colca Canyon is generally safe, as are Arequipa and Puno. However, don't walk alone at night, know where your money is, and educate yourself on the good and bad parts of town. Police presence has increased in Arequipa. Use only recommended taxi companies or have someone call you one. But walking around the plaza, even at night, is safe in Arequipa. Hiking El Misti alone is not recommended. Puno is generally safe in the tourist areas, but at night the port and the hills should be avoided.