In the loop is cool too but the OP was looking to use the tube drive distortion effect also and that is unlikely to sound great in the loop.   Certainly it is an easier setup to have the Pod in the loop and a couple of dirtboxes up front of the amp than 4CM but I would not write it off out of hand. 4CM does not imply amp models, quite the opposite.

Yeah, all true I'm afraid.  It's a trade off between tone and convenience.  The A/D Convertors and buffers on the HD series seem pretty good. I can discern a slight tonal change on my JVM when 4CM is in use but dynamics are pretty much unaffected with the levels set right on the hardware and in configuration. 

Pedals (with good or true bypass) will ultimately have less impact on the tone when turned off and you can mitigate the problem pedals with switchable loops but with 4CM you can completely change the positioning of your effects in the chain along with all settings and your amp channel (if Midi equipped) at the touch of a switch.  That is a trick that you cannot really pull off with pedals unless you want lots of duplicates.  For many people with modest requirements, this is not a consideration and if utubebenscott just wants a tube booster up front then maybe he would be better off with the Pod in the loop and a separate stompbox up front as you suggest.

For me, I like the versatility of 4CM and can live with the tonal impact.   I  have a homemade true bypass loop pedal so in principle could bypass the 'front of amp' part of the 4CM hookup using that and the 'FX Loop' part of the hookup by turning off the amp loop.  In practice I don't really feel the need.