Any reason why this can't be played with only two, what would have to change in the rules, what prevents it (if anything)?
I just recently picked up this game and had my first 3-player session. It was a little rocky, but I think we all learned a lot about the mechanics and ought to have a better session the second time through.
I think if your players are more concerned with having fun with the storytelling aspects of the game than they are with the win-loss mechanics, then a two player session ought to work out fine. Where it might break down is in competing over those quests. Since every matchup will be 1v1, they might get a little predictable. I found that even in a three player session, it wasn't that hard to keep track of how many cards each player was holding. Since the player with the largest hand will always win, the one with fewer cards might just skip the quest entirely. The only thing that shook up the contests in a three player session was wondering if the Writer would get involved and which side he would come down on.
For a two player game I'd recommend, at a minimum, incorporating all the optional rules. The more ways the players have to gain and spend story cards, the more difficult it becomes to know what the other player is holding.
Alternatively, you could deal out cards for the Writer and treat that as a bonus hand that can only be used by the player who's currently lagging behind on the Memory Track. If both sides are tied, then the Writer characters just fade into the background.
In my opinion play this game with 2 players will be a bit boring. Tt he best number for me is 4 players.