ok mephiston is an easy answer, power weapons, the dude DOES NOT HAVE ANY INVUL SAVEMephiston in a 1000 point army. We fought in a city scape, and he hid his Devastator(with Sigmun) and Vindicator behind Ruins and blasted my army apart as Mephiston butchered my Thousand Son, I gave up after the third turn after losing all but three of my noise marines.
I realized that I had nothing to deal with Mephiston and his 2+ save, and his I7 made him faster than any of my units in my list or army for that matter. I had even less to deal with the Vindicator(Which hid behind the ruins the whole game). And that I had much less to deal with a Horde army like the one my friend faced(88 models worth of ork in a 1000 point game).
if that vindi was behind ruins i hope to god you let yourself get cover saves cuz the way it sounds it may not have Line o' sight...also note that demolisher cannons DO NOT have barrage (not sure if BA dex has a the same misprint as C:SMs)
as for orks i think Tsons & CSM squads with flamers are your best bet. orks are what armor 5? get stuff AP 4 & lower