Don't know if this will work for anyone else, but it seems to work almost every time for me....
Once the game starts crawling (I'm lucky if I get a frame a second), I click on the Victory icon which brings up the Victory tab. I then slowly click on every other tab (finance, trains, etc.) and then close the popup. Magically everything returns to normal.
Usually there will be a slight pause when I click on the Goods tab and then I know everything will be alright. I'm assuming this is forcing a garbage collection or some such thing.
Also, if you are going to change the routes of several trains, first move the camera to a location with no city animation. I usually just click in the middle of the water somewhere. The game will slow down once I scroll back to a town, but while I'm in the ocean I can change routes with no slowdown.