I never tried to take the tyre wear off, so I don't know what other effects it will have.
I am still doing my Championship with the Jaguar, AI on hard setting and I'm glad to report I have won every race so far (had to restart it at Misano though

) and have reached pole in all races except Misano (again

) because stupid Morbidelli stole it from me by one hundreth of a second one minute before the end of the session (that's what you get for being condescendent and think you have the pole bagged already).
I'm facing now the last championship race, and it's my home race at Portimao. Funny I saw those cars racing exactly there this year (supporting race for the ELMS race) and I'm pretty confident I'll win it also (and get pole).
I think the real settings of the offline mode in this game make it truly great, you feel you are actually racing a real life series.
My usual routine (in a 1 event per night mode) is:
Free Practise 1 (30 minutes) - I load the quali preset tuning the team offers me and go for it with soft tyres, with the purposes of: a) learn the track overall layout and check the optimal braking points; b) understand what gears are too short/too long for what I need with my kind of driving; c) fine tune the car; d) check the AI pace.
I usually find myself, at the beggining, 2 to 3 seconds off the pace. Then I work on car setup and try to make my driving more precise. Usually I end Free Practise 1 with a good car for quali and topping the time sheets. I save the car setup at the end.
Free Practise 2 (30 minutes) - In this one I fit the car with the harder tyres, and try to establish (again) braking markers and if the gears need some tweaking for "race" condition. Don't care much about the time sheet since the AI cars seem to be - again - in quali mode. When I'm comfortable I consider my work done and press the "advance time" button. I also save this new setting.
Quali (30 minutes) - I load the Free 1 setup, go for it and when I reach P1 I advance time (5 minutes each time you press the button) one click, check the time sheets, another click ... etc. until the session ends. Only had to "go out" again twice.
Race (real duration, somewehere close to 15 laps) - I load the Free 2 setup and do it.
Of course this can change if weather changes (and it does, very often). At Misano both the practise sessions and quali were on a dry track and when the race screen shows up it's a wet race

so I had a bit of a problem there.
About car setup, I guess to each is own, but I usually like to have the brakes heavily on the front of the car (7 or 8), although this can be a problem in tracks where you have to brake while cornering (Valencia's last corner is a good example). However, when tyres start to degrade, at least you don't get afraid of braking because the rear tyres won't lock so easily.
Also, I usually put the downforce (only rear) close to maximum value. Again, I want the rear to be steady, it'll be my job to compensate the understeering.
I rarely tweak suspensions, accepting what the team suggests, but if I do, usually is to make the front a litle softer. Not sure if the outcome is the desired one, but I feel more comfortable that way.
Overall, this game has been both a surprise and a very pleasant experience.
Oh, and about buttons and FFB being lost. I never experienced buttons (but you must start using the game with the buttons on your shifter, it only recongnizes ONE controller, the one you used first), but losing the FFB happens often. Only solution, as you say, is to unplug-plug again the wheel to the PS3.