Pitchfactor signal chain placement quesiton

I'm running mine in the effects loop after the pre-amp (I'm not using any Dist/OD pedals, so it's all coming from the pre-amp). I have run it in front of the amp, too, though. Both sound great, but do sound different. The effects loop works better for me in my current rig. That's subject to change, though…

I don't think either in front or in the effects loop is any more or less valid than the other, but rather, what sounds best to your ears and works best for you in your rig.

Pitchfactor has delays in it.  Ever run a delay in front of distortion?  not pretty.  I have mine at the end of my chain because of wah sounds being delayed and reverb'd as well as distortion. I run direct at my church though with no power amp so essentially this would be the same as putting it in the effects loop.   I even run it in after my volume pedal so I can quickly pull down the guitar volume and prepare for the next note while my delays trail off.  My signal chain looks like this:

Jem Guitar -> Crybaby 535Q -> Digitech Whammy 4 -> Mesa Studio Pre (Mark II C+ Tube type distortion) -> Ernie Ball Volume Pedal -> Eventide Pitchfactor -> Direct Box (Direct Thru not cut) -> Sound Board

Here are some setting ideas here for normal guitar effects:
Diatonic with pitch set to Unison on Both A + B makes for a great stereo delay. Use Tempo mode and set A to a 1/4 note and B to a dotted 1/8 note (indicated by the dot after the 1/8) Shorten the decay on the dotted 1/8 note and lengthen, then set the mix to 50% and you'll have that U2 – Where the streets have no name delay setting.
The  H949-2 Can Micropitch those delays to create a chorus effect, and Using Crystals with A set to -2C and B set to +2 C With Reverb set to 80 and decay turned up high gives a really think and lush reverb sound.  Turning B up higher creates a shimmer effect. (not as smooth as a Strymon Reverberator though)
Harmodulator – Set this so the pitch goes up and set your expression pedal so as you move the toe forward, the mix increases and the rate of the pitch slows down to almost stopped.  This makes for an awesome intro to songs.

Ed, you've got a Mesa Studio Pre, too? Awesome… that's been my favorite "amp" for 18 years now, and the first amp I ever owned in my life that I didn't hate after 2 months. I still love it! Anyway…

You've got a point about delays after distortion… however, I actually really like what a good analog or tape delay sounds like in front of a Marshall (or similar). The repeats get cleaner… good for Live at Leeds type sounds. EVH may have used an Echoplex in front to boost the gain… I know that's greatly debated. None of that really applies to the PF, though. Not really the TF, either.

Sometimes (not always), the PF shifters track better in front. There are fewer harmonics and less compression, both of which are added by distortion and can throw off the pitch detector. The PF has a smoother sound overall in the loop, though.

I think a lot of it has to do with how much distortion, you know? Overdrive… crunch… high-gain… insanity…

I run it a bit early.   Currently I have compression and an overdrive pedal in front of it.  The position of compression could change and come after it, I'm undecided on that.  I definitely want at least one overdrive or distortion in front of it, and I probably will place a second in front of it as well (I have 5 of those in my chain).   At times I would want a clean signal coming into the Pitchfactor, at other times not.   Other non-distortion effects definitely come after the Pitchfactor, I am pretty convinced that is the way to go in that regard.