I've known several people to claim they can't get on with virtual buttons (and on-screen keyboards); they need the feedback of the physical buttons. Personally, I feel I'm not too bad with on-screen keyboards, but on reflection I see I'm much better with buttons. I could type faster and longer on my clamshell Zaurus than on my tablet, despite having a larger keyboard on the tablet.
I have very little experience with virtual buttons on trackpads as such, hence my reference to on-screen keyboards. The one device I have has a hinged trackpad which is no good to me for button pushes, the spring is too strong.
With the Twiddler, holding it in a fixed position with the strap hasn't worked out well for me, so it moves. Unless I can solve that issue, I'd need something to locate my thumb at the top. Another issue: Even with the physical buttons it has now, I find my thumb easily releases the modifier button before the key buttons. I have to be careful to release it later. I don't know how virtual buttons would work out in that regard. Virtual buttons could have one advantage: they could (hypothetically) be placed in a choice of positions. Num and Shift on the present Twiddler are a little bit of a stretch for me.
That's almost all I can say with my limited experience of trackpads. I think I found resistive trackpads more accurate than capacitative, but can't clearly remember any more. I don't like the way the pointer moves when I lift my finger off a capacitative trackpad or screen, it can be very hard to deal with, but I think it wouldn't be a problem with the Twiddler. Real pointer buttons mean I wouldn't need to lift off.
I was about to say trackpads are easier to clean than trackballs, but if you could find a trackball which would fit in the upper part of the Twiddler, I'm sure it would have a hole by which the ball could be popped out easily (unlike my one-handed trackball). That hole would be in an odd place for trackball design, it would be where the sensor normally goes; opposite the thumb. I don't know if there are optical sensors which can work on the side of the ball. Opto-mechanical pick-ups meet the side of the ball, but I hated cleaning those.
</ramble> That's all I've got.