I think some of this might (this is my speculation) be an issue with not having large, established cities of different ages and playstyles to test the fixes on. Sometime the patches cause issues when development of the city happened under old rules.
How old is the city you're having this issue on?
The reason I am believing this could be due to the age of the city is my newest city still has 3% unemployment with a population near 500,000, but my first city of 1.3 million struggles with about 59% unemployment. I will try the job opening by level stat because I keep forgetting to check, but the city had been doing well before patches.
There is another set of bugs mind you and I think some have to do with tourism. Tourism has been nerfed (inadvertently?) for a while and this will absolutely kill your entertainment and any other tourist-related industry. Tourists would seemingly aid profitability of your city's commercial zones too.
I also think a rebalance happened with industrial. It is suspected by a few players that the demand meter is not correctly functioning.