OK. So I flipped between Heroes of Hammerwatch, Everpath, and Dungeons and Dragons online. No issues at all with HoHW or EP.
Suddenly DDO started working again.
There's something not talking right between how it renders and how OBS detects when a game is full screen. Not sure what's going on there, but it just randomly decides not to work. It doesn't do it in the middle of a stream, but like when you open the game. Once it locks, it works, but next time you try to open the game it may not.
Weird.