What challenge unlocks are a must get?

[Krakkip]

I've hardly completed any challenges because I didn't really know what all they unlocked and some are pretty challenging but I was wondering which have the best items I should try to get.

[str8 up "ghoulin it"]

Complete family man, demo man, and waka waka.

[wckowalski]

Best ones in my opinion, though most of the other ones aren't worthless:

High brow unlocks a rune that doubles on consumables on the floor. Use it on the chest first room for an extra 4 items, of for great fun combine it with a blank card.
Solar system unlocks a rune that copies the d6 effect.
Demo man unlocks a card that can instantly kill any enemy, including end bosses.
Cursed gives a card that buys everything in a shop for free (or devil room)
Waka Waka and the Host unlock some great items (scythe tears, and added laser to your tears without harming normal tears)
Family Man unlocks epic fetus, which is way overpowered.
Speed unlocks a consumable that gives an alternate way to get into the Mega Satan fight.
Blue Bomber unlocks a pickup that gives you unlimited bombs for a floor.

[Karl Pilkington]

they are all worth unlocking, i think. except maybe the suicide king card, i never find that at a time when i could use it.