Modularization: modules have been separated from the core, dependencies between extensions have been minimized.
New multi-layer cache subsystem.
Changes in plugins API: simplified hooks, simplified plugin meta information, easy multihooks.
Massive code refactoring; all prefix finally changed from sed_ to cot_ and not just that.
HTML parsing support with HTML filtering. BBcodes are moved to a plugin, disabled by default.
Natural pagination mode: page numbers instead of database offset.
Automatic Installation and Upgrade system.
Built-in AJAX helpers and core AJAX support.
SEO: dynamic metas, titles, alts for images, title attributes, nofollow links, noindex pages, correct HTTP response codes.
Improved pagination with cutoms URLs support.
Contents internationalization plugin for pages, structure, index, tags.
Category structure is now global for the site and not only for pages. Forums module uses the structure instead of custom table with master/slave sections.
More elegant error and message triggering and display.
CoTemplate 2.5 with nested logic blocks, callbacks and advanced template compiler.
Skins are now called Themes, themes can have Color Schemes.
JavaScript/CSS consolidation, minification and gzip utility for higher page speed.
Backwards compatibility layer for Genoa plugins, which allows a subset of the old Cotonti and Seditio plugins to run on Siena.
New themes: Nemesis for development and new themes based on it; SymiSun-03 to demonstrate how nice it can look.
All HTML have been removed from PHP scripts, Resource Strings can be used to customize almost any aspect of the output.
Multiple logins (login from multiple browsers, devices and locations) support and still high protection!
Admin templates now form separate layout of backend area.
Private messages have got some Gmail-like features.
Validation queue displays items in the queue and has more filters.
Trash plugin has an API and displays items in trash can.
Password recovery is now a part of users module.
Improved search plugin.
Localizations have been modularized too.
jQuery 1.5, CKEditor 3.5.2, HTML Purifier 4.3.0 and other latest third-party components.
Comments and Ratings are now plugins.
Configuration, Authorization and Extension management APIs.
Form Generation API, File Uploads API, Extrafields API.
PDO-based database layer.
Import buffer which prevents data loss if en error occurs when submitting a form.
Special input functions for dates and pagination.
... and a lot more, I can't really list all of them. Most of the changes can be found in this Trac report.
