My wife and I have been talking about tabletop rp with just us, so I'm looking for a system for me to GM, with a setting she created. I tried to narrow it down in terms of how she’d like to play, and got: she likes classes, she wouldn’t mind having NPCs in the party, she’s fine with NPCs being simpler than PCs, she wants to approach it first as an actor playing a role, second as trying to maximize points, and she liked the sound of 4e D&D as a sequence of action set-pieces.
I wouldn’t try to play straight D&D4E in single-player mode -- the party dynamic is built into its mechanics at a pretty fundamental level. Even two players and one GM takes a great deal of work; one player and one GM is going to require so much low-level tinkering you’d basically be writing a whole new system.
My recommendation would be to look at systems that are explicitly designed for one-on-one play -- that way you’re not constantly going to be tripping over bits of the game that have unstated assumptions about party size baked into them. I’ve put together a recent post on the subject that you may find helpful.
In particular, I’d encourage you to think about whether you’re wedded to having one player and one GM, or whether you’d be willing to consider a two player co-op approach. Something like Ironsworn (discussed in the linked post) could be a good fit for what you’re describing if you’re interested in trying co-op.
