I suppose it boils down to which way you learn better, reading a manual or visually. Personally, I learn better visually so have never sat down to learn the shortcuts. Practically all the functions are available from the menu bars, which show the associated key short anyway, so for those functions you use often you will learn quicker (and only those you need to use).

The only one recommended to learn quickly is the A key (select / deselect all). If you prefer left click select to right click select, this can be changed in User preferences.

After three years, I have only really used the modeling, texturing and mapping functions and when I watch some of Jonathan Williams video tuts at Blendercookie I still find a function that saves me time.

As to whether to use 2.49 or 2.5, remember that 2.5 is still Alpha and a good few of the modeling tools still don't work as they should. I believe they are focusing on the Render side of things at the moment. I agree that the the interface is a lot friendlier now and you can alter the shortcuts in the User Preferences, so which version you use is personal choice.

Blender Foundation recommend that you still use 2.49 for serious work. By the time 2.5 gets on line for real it should be a short transition period but by all means play with it.

Tip: Keep the Wiki manual bookmarked......

Oh, and be prepared for a good few WTF? moments when you hit the wrong shortcut key and don't know what happened