I know what you’re going through too well… In my experience, 99% of the time project instability in Nuendo has been a result of plugins. Do you use ANY plugins that are made with SynthEdit? I’ve found these insidious: they often work fine while a project is small but start causing problems as the projects get bigger at which point it becomes difficult to troubleshoot. I’ve had to rebuild more than one project because of them. Ever since I decided to categorically avoid using them, my Nuendo has become remarkably stable.
Devs that use SynthEdit aren’t always forthcoming with that informtation, so it’s not always easy to tell. For now, one giveaway is that the plugin is only available for 32-bit Windows. I say for now because they’re working towards 64-bit compatability. If a plugin is available from the get go for 32 & 64-bit Windows AND for OS X 64 AU & VST, it’s extremely unlikely to be SynthEdit so you’re usually safe.
For the same reason, I also avoid using plugins in production made with Synthmaker/FlowStone, and plugins that are more experimental in nature or that come from new or unvetted devs. Of course some of these are interesting and sometimes offer something unique, but I’ll use them in isolation and prefer to export/process/import, or render the process and remove the plugin ASAP, or create a side project to use them in, rather than risk the stability of the main project. In fact, I use a special VST folder for these plugins to keep track of them.
But IMO, and I’ve mentioned this before, the other problem is that there no actual VST testing utility provided by Steinberg to the consumer to test individual plugins for stability; something like Apple Logic’s AU validation utility. This process only happens in Nuendo’s plugin scan and clearly some plugins that make it through that aren’t necessarily stable in all situations and the scan itself doesn’t actually subject the plugin to thorough testing; then again if it did, it would take the better part of a day or more to deeply test hundreds of plugins. A program that would exhaustively test a plugin would be very welcome; however, the other problem is that sometimes plugins can step on each other’s toes, like the SynthEdit plugins do, so testing in isolation isn’t the answer either.
If you can load a crashing project, you can try taking out plugins and saving intermediate versions to try to pin down the problem processing. I’ve managed to recover and finish a crashing project this way, despite the “gloom and doom” warnings from Nuendo. If you can’t load a project at all, try starting a new project and then load the problem project as an inactive 2nd project and again take out plugins, but I’m not sure if it will let you do that. Worse case, you start over completely which in my experience often ends up with the project being better than the original. 
Hope some of this helps…
