I have LMDE on two separate hard drives on the one desktop. The only downsides I've had have been some configuration issues on some updates. For example, on one update, automatic login was disabled - easily fixed, of course, by going to Control Centre/login window and resetting.
Currently, I have the 64bit version of LMDE as my default OS and the only issue I have is that despite doing a sudo update-grub after the installation, LMDE64 refuses to show the 32bit LMDE on boot

As it is not a "major" for me, I haven't yet tried to find a solution.
On the whole, I am very pleased I installed LMDE when it was first released and even more pleased that the 64bit edition was released. In my opinion, Clem and the other developers are "on a winner" with this release

Oops! for got to give you my computer specs.
Processor: AMD Athlon 64bit Processor 3500+
Memory: 2061MB
Audio Adapter: NFORCE - NVidia CK804