Can I safely clear AppData files?

I have a multi-hard drive computer with C being the smallest intended for system files only but Adobe keeps putting cache etc on there by default and filling it to capacity. I've been re-routing the cache storage to another drive manually but what can I safely delete from C after transferring? It's frustrating, it isn't that uncommon to have this multi-drive arrangement now as solid state drives are faster but more expensive than traditional hard drives and the no space on C issue is blocking updates.