There are several ways to determine the issue fairly quickly.
I would create a new project with a new name, and copy all files in the problem application to the new application and verify the problem still occurs.
Then I would start hacking away at the application, first removing files that have nothing to do with the file that was active and open when switching to design mode and the error occurred.
Then I would remove files and or code in files until the issue goes away, and see what is the last thing I do so the issue goes away or comes back.
It is a bit laborious, but it can reveal the issue fairly quickly and is straightforward.
If this post answers your question or helps, please mark it as such.
That's assuming it's a reproducable error. Not that it usually has anything helpful, but did you check the logs to see if there was anything useful in there?
If it is reproducable, you should log a bug with Adobe because you should never get an error like this, no matter how badly your application code is screwed up, it should never crap out your IDE.
IMO Design Mode is extremely useful but has quite a few major flaws, I hope they resolve these issues in Flash Builder but based on the beta, so far I'm not too confident.
(Sorry I don't have the link the Adobe's Flex JIRA site anymore, I used to have it in my signature, but Adobe decided to replace the forum software with this trash from Jive Software, and I don't think I can have such a sig anymore...)
I NEVER use design mode. I just work so much better in source mode.