Cities Skylines – Why Are Citizens Unhappy?

I think you are under the assumption that Highly Educated Workers cannot work the Uneducated jobs.

They indeed will eventually fill whatever jobs are available. At first they may not want to go work there, and the dirty industries may complain when they first go into business that there are no workers, but the Highly Educated will eventually go work there. The industry itself will display that they are "overeducated" — which doesn't appear to impact its performance any. So feel free to send those university degree children to the mines :D

Of course, theoretically if they went to work these lower jobs and you had some Highly Educated positions somewhere else, they wouldn't be available for those jobs. But then again you have no real way to control of who-works-where anyway.

Based upon information from online threads and in-game experience it appears that citizens will die at specified intervals based upon when the residential zone was created. There appears to be a few ways to combat this:

• Make sure not to zone in large bursts. Meaning that you should zone a few sections of residential as time goes on and not in one large block while paused.
• Ensure that you have plenty of Crematoriums and Graveyards that can easily access all areas of your residential zones.

Sources: first, second, third, fourth