Should I change diff ratio or tire/wheel size?

You need to stop and rethink this. From what I see the last owner wanted to slam the truck but maybe did it the wrong way. He threw out his high 24s for some low pro 22s... bad idea.
Your gear ratio is completely off now and also notice any vibration ever in your tranny?
I have my 379 slammed but I left the 24s on and just run low pros not high (from factory)... I also noticed your from NB. I say leave your gears alone and just go with 24s low pro. If you go as low as you wanted in gears you will be dragging your truck up those hills... manitoulin will be passing you on a hill
Also some numbers are just not going to work ... I am lucky my c15 gets good fuel and I have friends that drive slower and I still get better mpg and I got a flat top. Some engines even though it's the same year just do better than others.
If you do 5.8 to 6.1 and your doing 60 in your setup... you will do much better ones you do the 24s low pro

 

High flow mufflers will help. I put Donaldson high flows on my 2000 379 with a 3406E and picked up .3-.4s.

 

if you are running canadian weights the taller tires will kill u even more your boost will go up not down at 65 .we had a guy swap 3.73 to 3.55 he ended up having to go to lo pros to regain the .4 mpg he lost. if u run light disregard this reply. ask a scottlyn what they get for mpg with the 3.36s most are high 4s lo 5s

 

I dont know if this will help but i had a truck with 3.36 rears and 255/22.5 tires. I put 11r22.5 tires on it and gained 7mph @ 1500 rpm over what it was running.

 

When I put some Walker flow thrus on mine it made a huge difference in how fast it spooled up and EGTs. I basically had to re-learn how to drive it, at first I couldn't keep it below 1,500 rpms while getting up to speed.

My mpgs vary a lot but I could see .3 or .4 out of them.

That's your cheapest first shot.

 

talk to mr haney about your egr. he is the best. look and read his posts. full of info.good luck