Here is a Help Center article about speed issues, gives a lot of food for thought for both 3D and 2D slowness:
http://helpcenter.graphisoft.com/troubleshooting/performance/summary-of-typical-3d-speed-problems-2/
I think it is hard to say what is a size that is considered large, but I would say that anything that is hundreds of MBs in PLN file size is a large enough file so if the model is not handled correctly problems and slowdowns can occur.
But size in itself does not necessarily mean slowness. And reversely, a smaller file size does not mean it will be fast. I remember I got a file a few years ago, it was a few 10s of MBs but it was incredibly slow. Turned out it was because nobody had any idea of Library Management and its library was full of linked PLA libraries, thousands of duplicate objects, etc. which slowed down the whole file tremendously.
So one has to analyze the file, preferably based on the points mentioned in the above article to find the exact cause. Many times it is a single thing or a single user behavior or work method that is causing it.
As a closing guess, if you like to place PDFs and images in your Project files, those can really bump up the file size considerably if they are numerous, large and high resolution.
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