why do you want to upgrade?
I usually woul check the release notes first if there e.g. sth that would fix a issue you already have or new features you would like to have. And of course if there are any known issues.
We are running 22.214.171.1248 with epo 4.6.x. I think updating to 126.96.36.1998 could be worth. The 5.x agent also has some new features - but I think some (all? of them only work with ePO 5.1+ (again: Release Notes!)
Both agents 188.8.131.520 and 184.108.40.2068 works fine with both ePO 5.1.1 (Build 357) and 5.3.0 (Build 400) but have NOT tried agent 220.127.116.116 yet.
I just upgraded from 18.104.22.1680 to 22.214.171.1248 to resolve a big number of endpoint don't update DAT issue.