How about that underwater scene in the first Cameron Files - The Legend of Loch Ness. It drove me up the wall!

Jean

For me it has to be finding the key on the hidden belt of the guards in the castle in Mystery of the Druids. You couldn't even see the belt, let alone the key... so how are you even supposed to know it's there!!!

Ta-ra,
The Gremlin.

That damned cylinder at the beggining of Broken Sword 2

The bit in Simon the Sorceror where you have to pick up a rock. In a location. Made. Of. Rocks.

I didn't think the snake scale in the grass in GK1 was a pixel-hunt. You just had to see that a (reasonably large) patch of grass was matted, and then investigate closer. It was a great observation puzzle.

It was a bug and it was corrected in the DVD version. There was one other place in the game where the hotspot was 90

That was a timed maze. An abomination to be sure, but not really a pixel hunt. There was another thing like that in Dracula Sanctuary.

Best pixel hunt I've had was the one from "The Mistery.
The fourth level called "The Soulkeepers Grave"
should have been called the "Mistery Pixel Hunt"!!! Go ahead and test your skill...There are nine things to find. The Soul Keepers Grave

Inferno

"Lighthouse" is a pixel hunt even with the partial cursor highlighting available in version 2.

Thanks someone for mentioning the grapnelling in "Amerzone" - that caused me to give up first time round.