So I came up with some hard challenges for those that really want to test their skills:

1. Melee only challenge - Complete a mission using only melee weapons. No ranged lethal weapons of any kind allowed, including sentries, although non-lethal weapons (mediguns, milk, jarate) are fine.
2. Last stand challenge - Complete a mission by making a last stand at the hatch without leaving that area, except for money collection.
3. Hobo challenge - Complete a mission without a money collector. Accidentally picking up money while fighting is ok, but no deliberate collecting. Alternatively, if you're really hardcore, simply play without upgrading anything.
4. 1HKO challenge - Complete a mission without dying during a wave. Any player that does die during a wave has to sit out the remainder of the mission.