Pretty good question...
Well, since my FR campaign has been going on for 10 real years, and has been played in 2 editions, and I have players that are more than willing to accept major rule revisions...I guess the things I would change would be...
Implement more Pavlovian rewards for players to sit down and actually figure out the prophecies and portents which are core to the plot. Instead, faced with riddles and portents of doom, they've constantly tried to avoid them, thinking they were too hard. I've always tried to put out "good thinking" XP or other bonuses, but until last year, it just didn't seem to work.
I wish Arcana Unearthed had been out, as I would've have used that class/spell system almost whole hog, which would've meshed well in my opinion with how I see the Realms.
I wish I had been better at identifying the idiots and arse-brained players that I let into my run in the earlier years.
I've never had a LOT of house rules, more that I'm very tolerant of allowing third-party addins to my D&D. So that never bothered me. Third edition has changed that, in a generally good way, but in the end, that's why I decided to use the SRD to just incorporate everything I'm willing to allow baseline in my run. At this point, I've edited in every extra class, feat, and skill use into a personal home use SRD doc, and am soon on to handling the dreaded spells and psionics sections. That said, I wish I had done this a year ago.
Beyond that, I like my story, I love the backdrop of the Realms, I've always been rules strong with an allowance for on the fly ajudication, and the stories I have locked in my brain will entertain me to my dying day. So, I can't think of any other thing I would change. I certainly wouldn't change the poisoned ballista bolt episode...
The One Warlock