Blender's window management system has had major upgrades to allow greater flexibility and interactivity. Window manipulations work independently and update in real time, even while animation plays back.
Blender 2.5 supports multiple top-level windows, which can contain any combination of further subdivisions and editor areas. New windows can be torn off from existing areas (shift-drag on window splitter zone) and window layouts are stored in the .blend file.
Editor areas can be split and joined with the new window split action zone. Dragging the zone inside the editor area with LMB interactively splits a new window in between, dragging the zone into another editor area joins it. Alt-LMB dragging the zone swaps the area with another.
The new window manager also supports a generic system for further subdividing editor areas into regions for tool shelves, window headers, or split views. This allows (for example) a 4-way split 3d View which acts as a single editor, with common properties such as transform pivots and shading display types.
Blender's property panels have had a complete overhaul and reorganisation. The previous 'buttons window' had become disorganised after years of expansion, inconsistently mixing tools and settings, and needed major systematic revisions. The new property editor has been redesigned to be better organised, more flexible so you can more easily hide what you're not interested in, clearer to navigate, and easier to understand.
Blender's GUI controls have had a redesign, with better visual communication of type, content, selection and disabled status, and feedback for animation state such as whether a property is keyframed, keyed on the current frame, or driven. UI control appearance such as colour, font size and font decoration are customisable.
The new UI layouts are generated by Python script files, as part of the standard Blender installation. These layout scripts can be fully customised and modified in real time to allow you to modify the existing UI or create entirely new UIs from scratch. Because it's using the same system, user-created python UIs have the same capabilities and functionality as the default.
Blender's internal file browser has been upgraded with a friendlier design and more useful features. You can now switch between various (list/column/thumbnail) views, with background loading of thumbnails from any of Blender's supported image formats.
Quick filters by file type are available, and a new customisable bookmark list. Importers and Exporters now provide their settings in the left properties region, to adjust at the same time as file selection;