I definitely like using 221 midscreen for the meaty Quake and nearly safe totem setups, as well as in the corner for combos or into Quake reset. However, 22 leaves you at -9 and too far to throw (if you're staggering) and 221 leaves you at -7.
12 on the other hand leaves you only at -2 on block and in perfect throw range. Also, 122 leaves you at -6 which allows you to D1 contest combo start mids/lows of all of the following characters: Sub Zero, Scorpion, Kano, Kitana, Skarlet, Kollector, Johnny Cage, Baraka, Cetrion, Kotal Kahn, D’vorah. Of course, many will just go into their own D1 after 122 ends because they know they don't have a fast mid, at which point you can block and take your turn back, or flawless block U2 into a combo if you're godlike (still working on this myself). Lastly, if 122 hits it leads into a max range meaty Quake. The timing is tighter than off of 221, but the fact it's max range means that if the Quake whiffs, you're more likely to go unpunished.
Don't get me wrong, 2/22/221 has it's place! I just think as a go to string after D1 and D3, 122 should be the staple.
Edit: Previously I had said that 34 was the ideal follow up after a D3 on hit, due to it being high damage on hit, +1 after the 3 on block, and 0 after the 4 on block, but 3 doesn't leave you at the right range to throw and while you can mash D1 after 34 to get your turn back, you'll trade with characters who have 6 frame D1s. Because of this and because you have to be frame perfect to get the standing 3 after D3, I think 1/12/122 is actually the all around better go to. Also, you can get 1/12/122 after D1 so you only have to train your brain to do one stagger string after you confirm that you've hit with D1 or D3.