I'm running my Line 6 POD HD300 through the effects return on my Marshall Mg100hfx.
It seems like this is the only way it can sound good, however, I just have a small question. Some dude told me when using this set up live, I should use the preamp models on the POD. My question is.... why?

It sounds better to me when when I use the "Full" Amp, but I'm not sure how it will do during a gig. I've played with it at my first band practice using the "Full amp" and it sounded pretty good.
Ditch the POD, tweak your amp settings until you find a good tone, which IS achievable on an MG. If you don't like the MG's tone, sell it and get another amp.
Just experiment and use what sounds best to you.

I used to play my GNX4 through an MG30dfx. I used amp/cab modeling and set the MG on the "clean" channel w/neutral EQ. No matter what I did, it sounded muddy compared to running the GNX4 through a Behringer keyboard amp.

Eventually I got a JVM410h and 1960 4x12 cab. Now I run the GNX4 through the "in" jack on the amp and have the JVM set on the Crunch Channel with the "Yellow" gain stage. I'll still use some amp modeling, but bypass the cab models. The amp modeling and EQ work great for fine tuning, depending on what I'm covering. But mainly I use the GNX4 for stomp box modeling, like noise gate, compression, spring reverb, delay, vibrato/tremolo, EQ, Whammy, big muff, fuzz factory, and tube screamer. I could use the effects loop, but that takes longer to set up, requires more cables, and it didn't seem to sound any better.

Often the venues are too crowed for the 4x12 cab so for those places I bring along the old MG30dfx and the JVM head, and use the MG as a small cab for the JVM. I disconnected the built in amp and wired up a speaker jack directly to the speaker. Even with the cheap 10" speaker, the open back, and the cheap cabinet construction, it sounds great--almost as good as the 4x12. Just have to keep the volume [relatively] low so I don't blow out the 30w speaker, but then again I haven't been able to ever have the master volume above 3 on that head because I haven't come across a PA that could keep up with the vocals without feeding back.

So if you mess around enough, you'll find something that works for you. BTW, don't get rid of the POD. If anything, save yourself the hassle of moving the amp around; leave it at home and plug your POD directly into the PA through the XLR line out--just don't forget to use the speaker compensation. And make sure you can hear yourself; you might want to invest in a powered wedge monitor (which you can also drive directly through the POD). Or better yet, an in-ear system.