Results of some thinking:

A fundamental problem:

1. If the primary conflict for the player-character is finding a way home, then the player has to do something to get home. They need a way to gauge their progress, to understand how their current actions fit into the whole.

2. I have to create a strong reason for the PC to want to go home. This means either something has to be pulling him home (family) or something him has to be pushing him there (the world is dangerous, hostile). There needs to be a sense of urgency. This is sort of the polar opposite of the mentality I started with, which was one of exploration.

3. If there is some sort of known formula to get home, that breaks a lot of setting and characters. The first NPC idea I came up with, and one I want to work into whatever I finally do, is a pious man who thinks that he is being punished by God for some transgression, and he will be free when he has atoned. I want it to be believable that he could be right. If getting home is just collecting some number of MacGuffins then he knows that he is stuck because he cant kill the dragon and take the magic ring or whatever.
He could persist in his belief, but he would be less sympathetic and more... crazy.

An even more fundamental problem, now that I think about it:
-Predictable gateway behavior clashes with the the overall shape of the narrative and world.
-Unpredictable gateway behavior clashes with all the smaller scale stories and elements.

By unpredictable I mean, you can't tell the player "Go through that portal and get me 10 rat tails" when the story is built on the foundation of not knowing when or where a specific portal (namely the one home) will actually show up.
There is a solution for this second problem if you can come up with a satisfying reason for some portals to behave differently than others.