Just make all changes to the item's attributes and then call item.editEntity:

item = pywikibot.ItemPage(repo, 'Q123')
item.labels['en'] = 'English label'
item.descriptions['de'] = 'German description'

claim = pywikibot.Claim(repo, 'P456')
claim.setTarget(...)
item.claims.setdefault('P456', []).append(claim)

item.editEntity(summary='edit summary')

I understand it's possible to manually do it this way, but it would be much easier if pywikibot could do it internally. It is much easier to pass in a claim with qualifiers and references added than to manually deal with all of this yourself. Plus it requires knowledge of how the editEntity dictionary needs to be structured, which isn't readily available for non-trivial examples. The entire point of having objects is that instead of needing to go down low-level like this, we can use the higher-level helper methods.

Plus it requires knowledge of how the editEntity dictionary needs to be structured, which isn't readily available for non-trivial examples.

It does not, I'm not building any dictionary in my example. You first stack the changes by setting/appending data to the entity, then you call editEntity without the data argument.

I can think of one improvement, we could enhance the ClaimCollection (item.claims) with a method like item.claims.put_claim(claim) that would inline that chain of calls.

I think maybe another option is to add optional kwarg internal to addClaim/removeClaim/etc. Then those methods will basically do what your code example is doing but without having to setdefault every time.