My son was fascinated by KNP at 9 months old, probably because he wasn't all that mobile yet.
We did find that it was best in the mornings and late afternoons when we were likely to see game (herds of impala are more fascinating to little ones than a solitary lion

) and staying in camp, esp ones with swimming pools, during the heat of the day worked well for us.
He's currently 22 months old and if yours is anything like ours then frequent breaks will make things a lot better for you I'm sure!
They simply can't stand being cooped up at this age

.
If it were me going in with a 22 month toddler I'd stick to the South where there are more frequent facilities.
Lower Sabie is a lovely camp with a large deck overlooking the river and also has a long grassy area in front of the huts to the right of the restaurant which you could kick a ball around on with him to get rid of some of his energy.
Drives from Skukuza to Lower Sabie would probably be within what he could endure, especially as there is the Nkulu picnic spot for a break along the way.
At Skukuza there is a super day visitors facility with a swimming pool.
Pretoriuskop also has a pool and a nice large grassy area for running and ball play - and often some impala there too which would fascinate your little boy.
There are also lots of birds, but you may find some fellow residents in the camp take an exception to the little boy basic instinct of bird chasing

.
In all the camps/picnic spots you will be able to find interesting lizards, moths, etc which should be great fun for him to look at.
I'm sure after the plane trip car trips between the camps won't seem too difficult.
The major problem I guess will be curbing his natural curiosity when out of the car - keeping him away from water, possible snakes, etc.
I bet you'll all be sleeping very well at night

.
Other than that, just hats, cool clothing, high factor sunblock and of course mozzie repellent.
I hope you have a super trip and that he soaks up the experience