As a comparison, the game I've played the longest is 10 MB.and I'm in my 6th generation on that one. I only have a few played families though and haven't maxed out relationships with too many Sims like you do.
The game is supposed to be played however you want to play it but to me it seems, the file size and RAM usage isn't very optimal. I'm not saying it's how it should be but trying to find out the reason why your lots start disappearing. When you replace the lots in Willow creek, do they get their icons back on map view ? I've noticed that they are all missing
If your save game is that old, it's possible that it suffers from some old save bloating issue as well but I don't know how to get that down.
I would make a backup and try if if gets better if you play some families that aren't that important as unplayed. They will loose they're relationships though due to relationship culling.
Which lot did you have that error message on (where all the furniture got removed) ?