When Apple decided to hardwire memory and storage I was stuck with an old MBP with an 1TB drive I'd upgraded to and the prospect of paying a huge amount to upgrade a new MBP with the same size drive. Instead I looked to trim - viciously.
The first thing I did was ensure that I had 2 good TM backups because my intent was to begin erasing and moving files off my old MBP. My idea was this: There was stuff I didn't need but just in case, I wanted to have a safe copy. One of the 2 TM backups was designated Archive and I'd never backup to again. Its role was to hold everything "just in case". There was stuff I wanted to keep but didn't necessarily need to carry with me every day. These files I copied to a small portable drive and erased from my MBP. In the end, I had my MBP pared down to just under 400GB and I spent several months using it and making adjustments with some files moving off and some moving on. During this time I was backing up to a totally new TM drive (didn't want to touch my pre trimming drives, just in case). Finally I was satisfied and when I purchased my new MBP with a 512GB SSD I had a TM drive ready to make the switch.
A long winded way of saying, make sure you have at least 1 good backup of now and then disconnect it from your computer. Remember, a TM backup is guaranteed to have your now files, anything you delete from your computer is a candidate for TM to delete. Now start removing stuff. The only safe way is to go thru files by hand and when in doubt, keep a copy on another drive.