In my use cases, the 12.9 is much more beneficial. I mainly got it to draw, so I need that big canvas. But it's also great as a fill-in laptop when I want to be productive (e.g. at a cafe) but I don't want to lug around my 15" MBP (assuming I have the ASK). For that, the big screen is also very beneficial, especially when using split screen. The big screen is also great for when I occasionally use it as a second display for my MBP. Finally, the big screen is wonderful for getting immersed in movies and TV.
I find the 12.9 comfortable enough to use on the couch, but I don't use it there much these days. While in bed, I use an arm mount to hold my iPad while I read or watch movies/TV, so device size doesn't matter there.
12.9 is not great for these use cases: e-reading, taking notes without drawing attention, and always carrying around from room to room at home. But for those I bought and prefer an iPad mini. (Note- I don't absolutely need the last use case, but as long as I have the mini I like to keep it handy.)
If I had to choose one iPad, the 12.9 would have the least compromises for my use cases. But with the 7.9 mini combo, all my bases are covered pretty much ideally. The 10.5 size just doesn't have a place in my life at the moment.
I have pondered this question myself. As an artist you would think I would prefer the larger 12.9" screen, but I find it overwhelming and the 10.5" allows me to focus. I also like the ability to one hand while i sketch,which is a little bit more difficult on the 12.9". I also don't do full size paintings, I do more vector/logo design. It is funny though since you can zoom in and out, the size of the space you draw doesn't matter as much, a 10.5" inch iPad could draw the same resolution/size image as the 12.9". I think the 12.9" would be for someone needing a complete laptop replacement. The iPad for me is more of an artists tool!
Maybe it matters the type of drawing one does. I draw a lot of people and characters and some scenery, and I like to sketch loosely, so the bigger the canvas the better, as long as it's somewhat mobile. As far as holding it one handed, have you tried cradling the 12.9 in your arm like a clipboard? That works great for me. But it's all preference of course. Back in paper days, artists preferred all different sizes of sketchbooks too.
