Re: Haven't been here in a while...
5ER has:
Much improved layout and artwork.
Much improved organisation, making it easier to navigate.
Corrected known errata.
Inserted new errata (according to Steve this is because fans will have fun tracking them down).
Features from Sidekick, making the system more accessible to newcomers.
Expanded and clarified Power descriptions, incorporating much material from the old rules FAQ.
Some new Power Modifiers and other material from some of the other books such as Fantasy HERO and Star HERO.
An appendix containing the Size Templates which appeared in Fantasy HERO, Star HERO and The HERO System Bestiary.
The HERO System Genre by Genre document as an entire new chapter.
Extra coolness value!
The only rules "changes" as such are expansions of Extra Dimensional Movement and Trigger, so Sidekick shouldn't be affected in any way.