Similar to what TechGirl said, different things work for different people. But, based on my experiences... (this is copied & modified slightly from my UA post)

I have a 20" TravelPro (Crew, not expandable & it does have the "suiter" feature) and a 22" expandable Atlantic (replaced an ancient 22" Atlantic). I travel primarily with the 20" TravelPro. I pretty much only use the 22" if I'm checking my bag (rarely) or know I"ll be needing the expandable feature (also rarely), or if I'm flying UX or Eagle and gate-checking.

I prefer my 20" because it fits about anywhere (on mainline flights)...including under the seat in front of me (even on a 73x in Y, although not on an MD80 in Y due to the empower adapter boxes) in a pinch. It fits wheels in on all mainlines overhead bins except 767.

I bought the 20" a few months after buying the new 22" expandable Atlantic as I was having problems with it easily fitting in the overhead bins. My newer 22" Atlantic does fit wheels in on most mainlines, but the bigger problem I was having (sorry, I don't remember if it was on the 73x or the 3xx) was with it's depth (height of the bin) when relatively full (but not expanded -- when it's expanded, forget it as a carryon.

As to the difference between what the 20" and the 22" will hold? I've sat there packing & repacking back & forth between the two bags before and found that there wasn't THAT much difference between the two. Perhaps just enough room for an extra pair of shoes. (You might want to think about doing a trial run on packing what you're planning on taking for a 3-4 day trip in the 22" and then repack it in the 20" to see the difference.) However, on business trips I also carry a Tumi briefcase which has my notebook & all work stuff in it (it's expandable too, which has been a blessing many times), or for "fun" travel a smallish Kate Spade tote that I can keep under the seat in front of me for anything I might want to have handy during flight (or a small duffel if it's a longer trip).