I've had projects with literally thousands of topics. So I guess it depends on what you consider to be a large project. Some folks see perhaps 500 topics and think that's really large. So it's subjective.
The biggest issue I've seen in my own experience is that with many different topics you may see a slowdown when you attempt to create hyperlinks. But I think that report was from someone that had all their topics in a single folder. If you organize using folders you are better off.
Hopefully others will offer their own insights as to what they encountered.
Rick is right. It is subjective. Things like hyperlinks, bookmarks, DHTML etc. are all likely to cause performance issues when used extensively inside a single topic. For the author this is a minor annoyance but to the end user this is critical. You can get around these issuses with good topic and project design. What I think is critical for you is to sit down and plan out your project structure. Only then will you have a better idea of what is acceptable.
On a personal level I've not had a problem with projects of 2000 topics or more. One such project could take five minutes to open but it gave me a chance to have another coffee.