In the new theme, there is basically no different between large and small icons. On mac, there really is no visual difference. On windows it's about padding and margin, not the actual icons. Large icons are now 18x18 so old addon icons which are 24x24 are getting scaled down to 18x18 and look bad. Small icons are scaled up to 18x18 and look bad (although this will be fixed and will be 16x16). It makes no sense at all to have small icons that are 16x16 and large icons that are 18x18. Just dump the whole large icon concept and use the 16x16 addon icons everywhere.
There's another major problem with the large icon support in Firefox 4. Right now, a lot of addons just punt on the large/small icons and use small icons everywhere. This works because Firefox doesn't resize icons, it just uses them as is. If you scale all large icons to 18x18, you'll mess up all addons that use only small icons.