Essentially Nelly has several enormous sites running on a box that's a lot smaller than we would have specified but it already was in place before we took over support. We did hit a bug with SQL optimisation in messaging - the site had nearly half a million messages stored. I've not seen anything like that before.
At the end of the day, you can tweak all you like but if you have a huge site you may well need big hardware.
My magic wand is broken too