There most certainly are very noticeable issues playing it in 1280x800 (clipped parts of the levels/gui and misplaced elements) and to say that everything looks crystal clear no matter the resolution is, well, wrong. It depends very much on your monitor, how well it deals with non-native resolutions varies wildly from model to model. Just because it looks right for you doesn't mean the same holds true for everyone else.
Well in that case, I'd be very curious to see these issues, since I barely noticed anything while I was playing. Exactly what do you mean? All I saw was that the end-level pull cord was out of place, and the end-level goo tube didn't fill quite right.
What happens on your monitor when it tries to scale that isn't happening on mine? The edges of most objects in the game are rounded by design and there's some natural dithering no matter what resolution you run at, so I find it hard to believe you'd notice a big difference between native and non-native high resolutions. I'm not arguing you wouldn't notice a difference in some other programs, but in the case of World of Goo, the art design should preclude any significant pixelation or dithering incurred by running non-native. There should technically be a difference, but surely not enough for there to be a perceptive problem.
Those two problems are the most noticable ones, but I seem to recall clipped text as well when I was trying different resolutions (could be that this was happening when I tried 1280x720 instead of x800). These problems aren't bad enough to make it unplayable at all (unless you increase the vertical res further), but it certainly is noticable even though it probably won't bother everyone.
As for the quality of non-native resolutions, the image is quite blurry (very noticable with the lines that shows when trying to connect goo) and have less clear colors and contrast compared to how it looks in my monitors native 1680x1050. Also, scaling a 4:3 image to 16:10 makes the image distorted in that round objects no longer are just that.
Now I'm still enjoying the game immensely, but I would enjoy it even more at a native res.