Damn, I never thought there would be someone using such an old version of my plugin! :P
Anyways, there has been so many changes since 1.4.6 than I'm not even sure if making the jump from there to 2.1.4 can go without showing some side-effects since the way settings are being handled now differs a lot from what it was back then. I'm sure widgets will stay put right where they're now but some settings will probably be lost and you'd have to change it back manually.
I'd say you should move to 1.5.0, then 1.5.1 and then 2.0.0. Jumping from 2.0.0 to 2.1.4 should not cause any major issues as the core code of WPP is basically the same on 2.x.x, just a few new features and fixes. Again, chances are that some of the settings will be lost during the upgrade but in my opinion it should not be an important hit to your blogs.
I knew this day was coming, however I didn't expect it to be like this :P
P.S.: I strongly advise you to backup your blogs' databases before upgrading. Also, over 1000 blogs? Seriously? How do you maintain them? I barely could keep one and had to close it down because of lack of time to post and keep it fresh.
P.S.S.: I had no idea my plugin worked on MU! Just re-read your post and realized that all these 1000+ blogs are under MU! Do keep me updated with the results of the upgrade, alright?
P.S.S.S: Forgot to post the link to download the different versions of my plugin: http://wordpress.org/extend/plugins/wordpress-popular-posts/download/