Basically:
Rocks are the lost
Hearts are the lost
Pickups are the lost
Soul hearts are Blue Baby
Black hearts are Azazel
Tinted Rocks are Isaac
Golden keys and bombs are Isaac
The Floor is the lost
unbreakable rocks are Azazel
Bomb rocks are Blue Baby
All of the regularly coloured characters are the lost
about 30 items are renamed to "The Lost" description: "Lost"
And the title screen shown above.
I think that's it for now.

The Story:
The Lost and his Lost lived alone, on a lost on a lost. The Lost kept to himself, drawing losts on his lost while his lost watched lost broadcasting on the lost. Life was lost, and they were both lost. That is, until one day. While watching the lost, The Lost heard a voice from The Lost. He said, "Your Lost has become Lost, and you must make him lose all that is lost." So she stormed into The Lost's lost, and removed all that was lost. Then, once more, The Lost called. "Your Lost is still Lost. You must FIND him." Overhearing this, The Lost peeked under his lost's forehead and found a trapdoor. Before his Lost came in to find him, he leaped into the Lost.

Now you must fight the enemies in the basement and below, before they find you.