2.5.1 is a major step back in functionality and resource requirements as far as I can see. The posting and deleting routines are pigs, hogging huge amounts of resources and taking forever to complete on larger blogs (which means the code wasn't written to scale up, the results should be similar regardless of the number of posts in a DB at least until you reach the limits of MySQL).
The new admin interface is significantly less informative than the old one (but certainly does encourage you to visit more wordpress owned sites, blogs, and to add plugins to slow your blog down further). Losing the ability to quickly at a glance (without loading another page or two) to see current and scheduled posts is a real pain, adding work. More of the admin interface is about outside stuff and less is about my blog(s).
I have already found at least one and possibly two situations where queries are made against fields in databases that are not indexed, which slows them down tremendously.
The WYS ain't WYG editor still outputs it's posting in a different character set than the raw editor, which is a pain in the butt, as most sources that read the RSS feeds after see the UTF-8 characters twice and mess up the posts.
More features, more design, more garbled code... against the basics still not working right or consistantly from version to verion.