I would imagine that 2 Twiddlers would be just fine (just as using two keyboards with a laptop: Internal and external). They just send HID codes, after all, just as a normal USB keyboard.
As I (mistakenly) noted in another thread, I'm not sure of the Twiddler's use as a gaming device, though it may be good for toggle-type settings. In terms of mouse usage, it would depend on how well you work with a hat switch. You haven't bought a Twiddler, so for mouse use think of a pointing stick. The Orbweaver has an analog one, so you may already be used to something like it.
I'm thinking you need a cross between the Oculus Touch Controller and the Twiddler.
[Personally I bought a Twiddler for typing, and have use mouse and keyboard for gaming.]