There's no reason for this to suddenly happen! I haven't changed any content. Why would it take so ungodly long for the game to so much as start up?

Agree with Save Cleaner, even v1 if the OP is on Patch 1.69 as the later versions won't work, and on fixall if an Awesome user. On MC, in addition to looking for 20,000 weird items like diplomas and discarded pizza boxes, as said a Reset Everything from City Hall every few sim weeks can work wonders on a slow to load and suddenly oddly performing game. And I would also suggest Overwatch, ErrorTrap, and Traffic for ongoing automatic maintenance tasks if one expects to play a game forward for any extended time.

Unfortunately though, I believe the OP refuses to use NRaas mods because they are too complicated and not "normal." Though we never did get a definition of what an "abnormal" mod actually is. We can't really be of much help there, the game just does not perform cleanup tasks well all on its own.

I don't think I ever said "not normal". But so many things seem to hinge entirely on NRAAS and so many people seem to depend on it that it seems like it would be having to learn an entirely new program to play a game I already know how to play. At least that's the impression I get. I don't honestly have a head for technical stuff and everything I've seen makes it seem highly technical.

There a lot of reasons that happens. The game on it's own will eventually start lagging, having loading errors, etc. and eventually become unplayable or at the least too painful to play. Regular maintenance is needed to keep it healthy. That's where, at the very least, as nitromon and igazor pointed out, Overwatch and Error Trap (those only need to be installed; they work on their own) and Master Controller, are pretty much "must have mods". In addition to OW and ET clean up, MC has commands to clean out other junk that an unmodded game generates. Should you feel the NRaas mods in the first column fall under the "not normal" category perhaps some of the additional suggestions in the second and third column will help you out. Tips For Game Performance.

@nitromon - sorry didn't see you in there before I posted

I don't think anything in the third column applies at least, a far as I can tell.

Right now it's gotten worse though. I was sending my people back from a vacation and it's been stalling out on the travel screen for about an hour now, only at the beginning of the load (the regular stall is at the very end). I did try to run CC Cleaner but it refuses to open, saying that the file type can't be opened (despite that I know I ran it before...I have a history of having to reinstall the entire program in order to run it more than once).

Does a newly started test game behave better? If the broken return travel transition were the only problem, you could try temporarily turning all graphics settings in Game Options down to the bare ugly minimum and retry only after a fresh startup from just before they were to return home to reduce stress on the game. But it sounds like at least several other things are going wrong here.

Your basic choices here are probably to abandon that ongoing game entirely and hope the next one lasts longer or install Overwatch, ErrorTrap, and Traveler (and MasterController as mentioned above for the Reset Everything command) to see if it's not too late to fix this one and to help prevent this from happening next time. Of course you do not have to take the mod advice, but it's what helps more often than not for most of us who do not wish to keep starting games over or port our sims by way of the household bin into new environments, which itself is really just another way of also starting over.