When images are uploaded, I usually use a plugin (e.g. Imsanity) to resize the original to a more sensible size than some of the 10MP monsters some users like to upload - usually I specify max 1600x1600 which means I end up with 2MP photos at 1600x1200.
When I insert one of these into a post, I usually use a thumbnail size around 150x150 and then link to a larger version using a Lightbox effect.
The problem is that the WordPress editor only offers 3 automatic link generation options: None, File URL, and Attachment Post URL. Obviously the only option that will work with lightbox is File URL but this only allows me to link to the original 1600x1200 image. If I do this and someone is viewing the site at 1024x768 then a large portion of the image is off the screen and there is no obvious way to close the Lightbox windows.
I suggest that instead of the "File URL" button, there should be "Medium File URL", "Large File URL", and "Original File URL". [Since this would mean there are now 5 options, maybe it would be more sensible to use a drop down menu?]
At present I am forced to manually enter and test the Medium and Large image links every time I insert a thumbnail into a post. Not much fun.