The 3D View looks slightly different in Blender 2.5x:
The obvious visible difference is the addition of shelves: the Tool Shelf on the left, and the Object Properties on the right. You can toggle the visibility of these by pressing T for the Tool Shelf and N for the Object Properties. Alternatively you can drag the inner edge of the shelf to the window edge to make it disappear. Whichever way you do it, when a shelf is hidden, this symbol will appear in the corner of the window, and can be clicked to make the shelf reappear.
Apart from the above, operating in the 3D view is still largely the same.
However, some keyboard shortcuts from older Blender versions may not work any more. They may yet make a reappearance as development of the 2.5x version continues. But in any case, most of the operations are now also accessible from the menus in the window header, so keyboard shortcuts are no longer the only way to get to them.