If you're using the GT-6 for the amp models then plug your guitar into the GT-6 and then the GT-6's output in the amps FX return. This will bypass the amps preamp, thus letting you hear the GT-6 to it's full potential. If you only want to use the effect in the GT-6(no amp simulations) and use your amp for it's clean and distortion sounds, then it can be used in front of the amp or in the loop. They will both sound different. One thing to remember though. If you run it infront of your amp, i.e. guitar-->GT-6--->amp then your reverbs and delay's will not match up between a clean channel and a distorted channel. I sometimes use my PODxt simply for the effects, and run it in my amps FX loop. This is done by plugging my guitar straight into my amps input and plugging the amps "send" to the input of the PODxt and the PODxt's output to the "return" of the amp. This way, all of your effects will be fairly equal between a clean channel and a dirty channel. The only downfall to this is if your effects unit has some distortion models you want to use, they will sound like crap in this set-up.

A tip to remember that works for me... Distortion and wah need to go infront of the amp, Time based effects (delay & reverb) are best in the loop, and modulation effects (chorus, phaser) sound good in the loop also. The time based effects and modulation effects can be placed either before the amp or in the loop, but will give you different sounds in both places. It's all up to personal taste, and I suggest trying out different way's to find what works for you.

I have 2 different effects setups. One I stated above: guitar--->amp-->FX send--->PODxt--->FX return
The other uses indevidual pedals: guitar--->volume pedal--->wah--->overdrive--->amp->FX send--->chorus--->delay--->reverb--->FX return