Things to check:
Plugs, a set of NGK iridiums would be good plan If replacing.
Are you running a factory air filter or oiled type? Clean the mass airflow sensor regardless.
Make sure air filter is clean.
Not sure if the S has the same issue of coil packs failing, if so coils should be changed out.
How many miles on your Cayenne?
Are you running the stock size tire for the vehicle? Why I ask this, if your running a different diameter tire it will throw off your readings for that trip computer.
Biggest thing that affects poor mileage on FI engines is a degraded O2 sensor(s), mass airflow sensors, regular tune up items (plugs) and obviously driving style, excessive idling, and speed
Hope you get it sorted out.

 

I find ETOH corn fed gas the worst! When towing I get less than 10 MPG on ethanol but with real 100% gas I see up to 13.65 MPG towing 7,600 lbs.

This is after EVOMS modified mine for 25% greater efficiency and power.

Non-towing, I saw an average of 13.8 MPG city and 15 MPG highway and maybe 21.5 MPG on Michellin Diamaris at 55 MPH. After mods I got just over 18.4 MPG city and 22 MPG highway ***** footing it on off road tires.

However, it is just too tempting and all too often safer to get on the throttle. So, my mileage varies with my foot. Now I am resolved to enjoy the ride and be safe over eveything else.

 

True... to a certain point...

My Carrera 4S averages over 20 mpg, and it provides more joy than my Cayenne!

 

I changed plugs few month ago,but I put in Beru plugs, for which I think that they were not the best choice. So if NGK iridiums would be better choice, I'll change it again.

I cleaned MASS sensor few days ago, and I'll see if there is any difference.

Coils, and filters were also changed few month ago.

Cayenne has little more than 90.000 miles.

Yes, I running stock tire dimensions.

And at the end O2 sensors. I thinking all the time If they could get tired through the years and they don't do his work like they should.
But Like I said, I don't know if that could be possible or not?