Front page looks too busy at 1280 px wide. I can't quantify why - maybe it looks too appy rather than like a page. I used to rant a lot about Flickr showing me 500 px wide photos with oceans of whitespace on my large screens - now it looks like they've gone overboard in the other direction...
Photos in different styles don't look great mashed up right next to each other on my photostream. Old design had an option to show them big as one column, or smaller with more whitespace around them.
The default photo height on my photostream is also lower than on the old big one column setting, which makes particularly my vertical photos look worse when you're scrolling by.