Hi, I personally have better experience turning off the cab sims, but .. try it out .. you may find something you like.
Also, ensure your level switch on the POD is set to Amp, I find that works better
There's no right answer for this. It depends on you and your patience and ears for tweaking sounds.
If you have an amp nearly flat (not your case), that doesn't provide it's own sound (the opposite of a Vox or Orange for example, that are very unique amps with their unique sounds), you should take wscottd16's advice and turn off the mic/cabinet.
On your case you already have a cabinet and your speaker. It's got the volume (in liters) of your combo that provides you a balance on treble and bass adding the specs of it's speaker with the impedance, the size, frequencies and other things. If you have patience and good ears I'd recommend trying using mic/cabinet simulation (which is my case). It's hard to improve and re-amp your sound but if you take a good time on this you'll probably get great results.
An example: I'm not a Vox's fan. But if I had a Vox I'd surely use mic/cabinet simulation in order to avoid that muddy thick sound I hear from a Vox. I'd try to get more depth.
Another example: If you want to get a clean sound that doesn't sound like a Marshall but something like a Fender (the old ones) you'd try a mic to provide you a more bright sound.
It's up to you, your time, patience and ears. If you're that kind of player that just want to plug, set a few settings and get a great sound... playing through your combo... I wouldn't use mic/cabinet.
If you want to try a more advanced tweaking on your sound and have the time and patience, give a try using mic/cabinets. Start using an amp. Change the mics to a regular 57. Change the cabinets... hear the difference on the Marshall ones, Mesa Boogie's... try to figure out one that would give you what your Marshall combo doesn't. Than at the end, change the mic distance to understand the difference... but don't start tweaking changing lots of pre-amps. Use only one with several different cabinets and mics, to hear the difference. If you get excited on the possibilities you'd get, start tweaking! If you get bored and feel it's gonna take lots of time, just turn off the mic/cabinet
+1 to wscottd16 and birro.
As you can see there is no wrong way to do it. I personally would leave the cab and mic sims off so that the true sound of your amp will complete the tones sound. Although as birro mentions, using mic and cab sims can help to tweak your tone to your liking.