Yeah I've tried Zepto as a drop-in replacement for JQuery once ... a long time ago. The results were disastrous (everything broke!) but I guess I'll try it again
It's still not a drop-in replacement, but it's close. You need to include more modules than just the core for eg. ajax or transition effects (the official modules are all available from http://zeptojs.com and/or the github linked there). I maintain a pretty hefty Backbone based web app where we use Zepto for mobile/non-IE to save on file size, and serve the exact same code but with jQuery for IE. In about a thousand lines of code, there are only 3 or 4 edge cases where the code paths diverge for a line or two, and they're due to IE peculiarities rather than Zepto/jQuery conflicts.
