Okay, so here are some things I've been noticing on my latest read-through of the books.
To start, The Lord Ruler was an important person. By staying alive, he somehow prevented Ruin from sending the Deepness upon the land. It was only after The Lord Ruler's death that the mists started coming during the daytime and killing people.
On top of that, The Lord Ruler knew what was going on. It's the only way I can see his justification for his comments at the end of The Final Empire. He had been alive when the Deepness ravaged the world a thousand years ago, and he was actively stopping it.
This is all a very complicated system. The mists are presumably the Deepness, a tool of Ruin, but the mists are also repelled by Hemalurgy, which it seems is also strongly affected by Ruin. Perhaps what happened was The Lord Ruler made Hemalurgy when he was in the Well of Ascension to stop the Deepness. (Explaining why Hemalurgy pushes away the mists, as it was created to prevent their harsher side . . .) Then, because Ruin was trapped within that very Well of Ascension, it gained a foothold in Hemalurgy. It would lend credence to The Lord Ruler's comment about Hemalurgy being "endowed fabrications" and solves both why Hemalurgy repels the mists and why Ruin can speak to Hemalurgists. Any evidence for or against this?