RedHat uses pretty much completely different GUI config tools, Mandrake develops their distro aiming at new/Windows users while RedHat develops mainly for server/unix-experenced users. A lot of the config file placements are the same (I hear, I've never actually used Mandrake =)) and It's not terribly hard to find your way around.
The only way to be truly distribution agnostic is to learn how each core package functions (and even then certain ones like ifupdown has very different semantics on Debian than Mandrake or RedHat will function differently) and ignore the flashy setup tools. One of Linux's biggest benefits is the infinite ways of doing things, but it can also be a PITA sometimes.