I have just hit my first serious issue with WordPress and for someone that enjoys Ajax this is a biggy.
I have an Ajax request that is taking 1.5 seconds to complete while using the Ajax API.
If I take the same exact code and run it with a custom script(no WordPress) the Ajax request takes merely 150 milliseconds. This is not an exaggeration
If you look at the very first comment of http://wp.smashingmagazine.com/2011/10/18/how-to-use-ajax-in-wordpress/ and the conversation that follows you will see that this slowness is caused by the fact that on your request, all of WP is loaded...
I am hoping that there is a solution out there that will make it possible to make Ajax requests while not loading all of WordPress.
What are your experiences with speeding up Ajax requests with WordPress?