I personally prefer the 24-fret design. I think this is because the neck is longer. I grew up playing Strats, so the transition to the 24-fret PRS was easier than to the 22-fret model. I do have a 22-fret Hollowbody, but I prefer my Custom 24 for playability.
Both the 24-fret and 22-fret models are a 25-inch scale length (excepting the Santana, SC 245 and a few other models). This means that on the 24-fret model, the bridge is situated closer to the neck, and the neck is longer to accompany the two extra frets. To me, this makes the neck feel a little more like a Strat neck, whereas the 22-fret necks feel more like a Gibson.
The rotary knob... well, PRS dropped it in 2011 in favor of the 5-way blade switch. Most people prefer the blade; it's easier to know exactly what setting you're on than with the rotary. But personally, I prefer the rotary, partly because it just plain looks better to me, and partly because new layout with the blade switch moves the tone knob to a weird spot, but also because I preferred the switching options on the rotary (you can't get the two inner coils in series or the two outside coils in parallel on the blade switch).
I also love the wide-thin neck (updated in 2011 and rechristened "pattern thin"), it just plain feels better than any other neck shape I've ever played. Most 22-fret models don't have the wide-thin neck shape available as an option.
