Sounds like its time to call on support, you could try opening a new empty workspace and copying all of the old workspace content into the new one.
I've seen several workspaces of that size but never had any problems like you describe.
I would first try re-installing FME and see if that helps.
If not, open a new workspace and copy-paste the old workspace contents into it. Save and see if the problem goes away.
If nothing else works, consider sending the workspace and log to Safe support.
Yep, anytime something crashes definitely contact support (safe.com/support)
nb: What format is it? Is it GML/XML/KML? I've recently had problems with a crash trying to add that format (when I check the parameters) but we can't replicate it and no-one else has ever reported it.