Before you do anything drastic, and yes there are things we can do, I recommend checking the backups folders. TS12, T:ANE, and TRS19 which i know you don't have yet, all have backups folders with the default setting to keep backups for 7-days. This is a backup of every route you edit, every asset you download, and anything else that is "touched" in Content Manager, including just opening the Config.txt file to take a look. The only exception here being that TS12 has a viewer instead of the need to open the asset for a look at the config.txt. The problem is these backups, while really are helpful in the times of need, and yes I have referred back to them on occasion, do add up to gigabytes of data.
Now the data structure for TS12 versus the newer programs is a bit different. TS12 stores its data under the same folder as the program in a folder called user data. The program is usually installed in C:/Program Files (x86)/N3V Games/Trainz/TS12, or maybe it's .../N3V Games/TS12 (I can't remember which). Under the TS12 folder is a folder called User Data and under that is Backups.
Within the Backups folder are folders that are in the DD-MM-YY format. These contain the daily changes and in addition to these is temporary saves in the Backups folder its self.
T:ANE and above puts the User data in a different location, usually C:/Users/{your login profile name}/App Data/Local/N3V Games/TANE/ followed by some folder named Build xxxxxxx where the xxxxxx equals some alpha-numeric sequence. In that folder is the similar Backups data structure.
The contents of these backups folders can be deleted, although it's good to keep a day or two worth. Remember this maybe 2 or more days' worth, but if you only use TS12 once a month for example, you'll end up with two backups with one for each month. I hope I explained that clearly.
Within Content Manager under the Misc settings in TS12, you can limit the number of backups to a lower number, with 7 backups being the default. The similar settings is available in T:ANE Launcher- Settings/Dev tab. The number of backups to keep is up to you and how much of a risk you want to take. I keep 2-days' worth of backups and then periodically clean those out if I don't refer back to anything in awhile.
Now as I said you don't want to do anything drastic, but you know you can move TS12 pretty easily to your much larger drive? To create more space, copy the TS12 folder from C:/Program Files (x86) folder on the C: drive to your much bigger hard disk. You'll have to fix the short-cut, and maybe fix your firewall, but things will work fine.
T:ANE and TRS19 allow you to put the data on another drive while putting the program on another. Like you I have a much smaller SSD, and I put my T:ANE and TRS19 programs on the SSD, but store my data on my hard disks. This is matter of adjusting things in the Settings on the launcher and we can help you with that, and there's an article available on how to do that right on the Launcher under Installs.
Hope this helps.