Welcome to the board. Big dilemma to start but for plin simplicity and choices of bullet weights I would favor the 6 MM. I personally believe it is more flexible and being able to obtain dies also will give a push to the little one.
We sell a bunch of both and build all the barrels for SHARPS in the 25X45. I suppose I'm biased as it was my first non-223 cartridge I used in IPSC though neither is a wildcat ta this time thanks to SAAMI a few years ago.
The best firearm for self defense? Any loaded one will do.