My girlfriend and I do this regularly with d20 based systems and I'm sorta in the process of doing it for a bunch of other people and it doesn't take any more monkeying than running for a group of players, really. When making encounters, combat or otherwise, you try to balance them so that encounters are not overpowering but still a challenge or at least meaningful, and there you are. You might cut back a little on save or suck abilities and you might make sure they have useful NPCs or GMPCs with them just in case, but even solo games are perfectly doable and enjoyable. The most important issue I've noticed is not tied to system: if the player is stuck they don't have other players to help come up with ideas. That is the single greatest complaint I have and have heard about 1 on 1 games.