First, thanks for the feedback. I'm glad you found this useful. Second, I'm no longer using LMDE. I switched to Mint 16. The reason for that was that some of the update packs in LMDE broke my USB installation and I had to start over, several times. I still like the concept of a semi-rolling distro based on Debian, but find that Mint main "just works" and gets out of the way so I can just use the computer as a tool.
That said, I think I can answer some of your questions. Others may want to chime in.
Has anything changed in the last year? I can't say, since I haven't used the latest version. The biggest change before that was the new label needed for the persistent partition, which I was fortunate to add to the tutorial.
Does the USB have to be blank? In my experience, it does not have to be blank. I have used and re-used USB drives with data on them to install and run multiple distros with Unetbootin, and have never lost a file.
Can you run multiple distros from the same USB drive? I think it is possible, but it might not work well with Unetbootin. Unetbootin writes menu files and folders using the same labels every time it installs a live distro, so if you use it to install a second one, you might inadvertently overwrite something needed for the first one. I've never tried that, so you might want to experiment and report back, or someone else can chime in. I do know you can install to USB as if it were a hard drive (do a full installation), and then GRUB takes care of multiple distros on the same drive (of course, that involves partitioning the drive as you would a HDD or SSD). But in my experience, a full install on a USB drive is painfully slow in operation. You're limited to USB throughput - better with USB 3.0, but not really useful for day-to-day work.
Can you create multiple target persistent partitions for different LMDE versions? I think so, but I haven't done this, either. This would be more involved than just changing the syslinux.cfg file to add persistence (and somehow adding a label for each target persistence partition). The "live-rw" hook is somewhere else (vmlinuz? preseed?) and would probably involve translating from hex, rewriting those labels, and recompiling. Again, I've never done this.
I would suggest carrying a separate USB stick for 32-bit and 64-bit versions of LMDE. You can load both of those up with both Cinnamon and MATE and select the one you want at login. If you want to do everything from a single stick, I'm afraid you'll need more programming expertise than I can provide.