A while ago I read a few blog posts about running the sqlite vacuum command on the Apple Mail internal databases to speed things up, and it dramatically sped up my Mail, I saw that Firefox also uses sqlite for a lot of stuff, so I tried this after upgrading to 3.5, and it definitely sped things up even further, so here it is, quite Firefox and run it and re-launch Firefox:

find ~/Library/Application\ Support/Firefox/ -name \*.sqlite -exec sqlite3 {} 'vacuum;' \;

For other OSes just change the find path to whatever you use, like ~/.mozilla for Linux.

After I did this I noticed my del.icio.us extension is a bit messed up, so I re-installed that add-on and everything’s fine.