There's various bits of data we store in internal fields for references and stats that can matter. It's doable, but I can't give you a definitive "it won't break" answer for your setup, since the product doesn't expect to have data pulled out from underneath it. We do delete review request data when a team account is cancelled on RBCommons, but those review requests are distinctly partitioned into Local Sites, so it's a little different. Plus we have our own logic handling parts of this process.
I'd say if you're going to go ahead and attempt deletion, make sure you're keeping long-term backups, in case things go wrong. I know your install is large and many people depend on it, so for liability reasons, it's just not something I'm able to encourage.
The biggest amount of data in the database is the diff data, and our diff de-duplicating/compression in 3.0 should really do a *lot* to address this. It will combine multiple entries for the same diff content into a single entry, and compress it with bzip2, reducing the size greatly.
Deleting older review requests won't reduce the size of the diff data at all, so that's also worth mentioning.
Christian