Earlier this year we decided to switch TopBits from a 160px sidebar to a wider 250px sidebar. The main purpose was to make the "Latest Forum Posts" module look better. This also enabled us to use a 250x250 AdSense block in the sidebar.
I figured that this would be great for CTR. Wider ads almost always outperform narrower ads. It's one of this useful rules of thumb in ad layout.
Eeeeerrrkkk... CTR for the 250x250 was just under half that for the 160x600 ad in the same spot. This appears to be an exception to the rule. We switched back to 160x600.
But wait... there's more...
The 160x600 ad unit attracts better ads from advertisers. As a result, even though CTR is double, eCPM is more than triple.
The moral of the story? Test everything. Assumptions will kill 'ya.