Pandora's box is very easy when you have good gear.
Just get the Legendary lure a bunch, get the legendary drops. I did it without losing 75% of my groups health.
The loot from Pandora's box is terrible.
Warrior, Rogue, Ranger, Cleric for dungeons. Warrior takes the punishment until he lashes out, Ranger and Rogue get their quick shots in, (Later on, they're usually 1 hit kills) and Cleric manages everyone's survivability.
Challenge 21 had me for a while, and I'm sure it had everyone else. Use a squirt tower first, upgrade it as much as you can. Block of the side paths to make the enemies go to the center. Put your first squirt tower there. Then, upgrade and expand to 2 sniper and 1 dart towers. Make sure ALL ARE FULLY UPGRADED