My second-favorite tower-defense game, Warstone TD (on sale for $7.49 from $15 on Steam), is amenable to playing with one hand. It's all mouse-driven (with optional keyboard shortcuts), and also works well playing solo.
I just tested and my favorite tower-defense game, Deathtrap ($20 on Steam, but IIRC it falls to $5 occasionally with seasonal sales), works with one hand but not as well as Warstone. It plays third-person and some of its actions are activated with keyboard shortcuts (1-4 and Q in particular) that would require reaching across the keyboard; the num pad doesn't work for the numeric shortcuts. So it would be playable, but somewhat more difficult as reaching across the keyboard would mean slower reaction times. It also is at its best when played co-op with friends instead of solo.
Conversely, I've played Orcs Must Die, but was not a fan - to me it was too fast-paced. I also don't think it would work well with one hand as it is a mix of FPS and tower defense, i.e. WASD for movement and a mouse for aiming and actions.