I think it would have to be a point-buy system, like GURPS is. The setting would be completely up to the GM and the players. Why not be able to play in the period after Sazed's Ascension? Or anytime?
I think it would work best to have an ordinary, generic system, plus the ability to use your character's development points to buy certain abilities: Misting, Mistborn, Feruchemist, Feruchemical Misting (only exists post-Sazed's Asc.), Hemalurgist. Hemalurgists can get their abilities in several ways: they can get a single random spike, or they can be a Steel Inquisitor, Koloss, or Kandra. Although koloss may not be entirely sentient, so they might not be very fun to play.
Ultimately, it's the GM's responsibility to enforce things like Feruchemists being Terrismen, Hemalurgists being influenced by Ruin, Skaa mistings/mistborn being very rare and hunted by the Steel Inquisitors, and Nobles trying to figure out who is a misting/mistborn.
If you want to do a class system, I suggest this:
Basic Classes:
Skaa (With thieving, stealth, underworld contacts, crafting, and merchant abilities)
Noble (With diplomacy, contacts, merchant, scholar, etc. abilities)
Terrisperson (Spying, scholar, contacts)
Kandra (Spying, stealth, Blessings give bonus to strength&speed/senses/intelligence/emotions, speed for forming a new body--must serve Contract) (Kandra couldn't be a prestige class because humans don't become kandra through hemalurgy; mistwraiths do.)
You could also replace Skaa, Noble, and Terrisperson with Thief, Soldier, and Diplomat or some such thing.
Prestige Classes:
Obligator (from Noble or very, very well-connected Skaa)
Steel Inquisitor (from Obligator)
Crew Boss (from Skaa or Kandra)
Misting Specialist
Misting Savant (from Misting Specialist)
Trained Mistborn (must be Noble or have a trainer)
Keeper (from Terrisperson)
Sorry if that's too much. I really enjoy coming up with ideas for things like this.