has anyone built out logic to flag whether items on a sales order can be combined into one package?

You mean fulfillment items into Package records?

Opposite I guess, packages into fulfillments. Like if I have 2 order line items and they can be combined based on their Package and weight, can I create some sort of flag, so we can tell our shipping integration to only print 1 label

Well the flow would be sales order->fulfillment->packages. The only way you can get an accurate count for figuring out how many you can put in a package is to first fulfill the sales order lines.

I can't say, just source the value of the item line package onto the SO and do some sort of look up on all the items and check a box if one of them say, doesn't need a label and add its weight to the other line? Before fulfillment?