It's all a possibility. Try 'em out and see what you like best. The only and most important advice there is. After all, you have to like the sound!
Onto the differences, as is implied in the names Series simply puts out the sound and cabling puts it through its various pedals/rackgear/whatever. Paralell also does that, but when it returns it is mixed with the original sound. In short... Series is perfect for tonal/pitch alteration (distortion, wah, equalizers, whammy, detunes, etc.), paralell for time altering effects like chorus, flanging and delays.
As to why put the pedals in the loops instead of in front of the amp? Where do you get your overdrive? If it is the amp, and you use a Reverb pedal for example then your reverb is being overdriven as well. This may sound like a tonal experiment, but most of the time it is cringeworthy. Put the Reverb in either loop and the reverb is not overdriven... Sound is nice
If you get your overdrive from a stomp box it doesn't really matter. You can try the experiment by placing the reverb before and after the stomp box though.
My setup is as follows: Guitar > Wah > Whammy > Overdrive > Amp >(series) Volume > Multi effector for reverb, delay, mod > Amp (return).
My overdrive mostly comes from the various amps and for solo moments I pump up the volume by switching on my Tube Screamer. Clean solos with the Deluxe module are boosted by pressing Boost on the multi effects unit. The rest sort of speaks for itself.
There is a mix knob for the Paralell loop. Pushing that all the way up to Wet only means you just created a Serial loop. Also don't put Tuners in the Paralell loop; my multi effects box has a built-in tuner and it was not silent because of the Dry part in the sound loop (just a simple tip).
Good luck, and happy tweaking.