I don't know much of the Rhineland, since I live in Southern Germany.
There are several cultural differences between the Rhineland and Prussia. For example, that the Rhineland is mostly catholic. (In the Weimar Republic, the catholic "Zentrumspartei" was strong in the area)
As far as I know, the population never really identified with Prussia.
There was the term Musspreußen (German Wikipedia:
https://de.wikipedia.org/wiki/Musspreußen) (which could be translatet roughly as "have to be Prussians") for the inhabitants of the regions which came under Prussian control, but never really identified with Prussia.
I see some potential for resistance in the 1840-1860 if you use political Catholicism and if you create an earlier "Kulturkampf" before the German unification or the war of 1866. (
https://en.wikipedia.org/wiki/Kulturkampf)
If you want an independent Rhineland, you could also use the French Revolution to create a successful Cisrhenian Republic.
Another option would be to avoid the 1866 war and the 1870/71 war (so no annexation of Hannover or other areas which could link the Rhineland to the rest of Prussia) , and slowly create more and more differences and conflicts between the Rhineland and the rest of Prussia.
Here is an (German) article about the unification of the Rhineland with Prussia:
http://www.deutschlandfunk.de/koeni...nlande-mit.871.de.html?dram:article_id=316206
It seems that parts of the Prussian Government thought that the area is far to liberal and had an far to high influence from Revolutionary France.
So there are cultural differences, but I never heard anything about real resistance.
In general, I see some small potential, but it doesn't seem to be enough to create an independence movement for the region.
Use either confessional differences or an revolutionary neighbor.