Generally it was completely painless but I did have two teensy problems.
1) EDToolBox started producing error popups which would steal input focus away from the game at the exact moment when I was dropping out of hyperspace and plummeting in towards a star. Eventually I had to simply comment out the code which did automatic system data updates.
2) The vertical sync option in the NVIDIA control panel (which I had checked specifically for ED because it got rid of some slight "screen tearing" which the in-game vertical sync didn't) stopped working.
Note: those spammy prompts (to review your security settings?) that you're getting will eventually stop giving you the option to ignore them (this happened to me at work last week, forcing me to take the update).