Primary path: Resolve

Aftershock is by far the best keystone on Thresh. It has a great synergy with your Death Sentence, because you can jump in so it reactivates right on the enemy making it easier to get a kill for your teammates.
Guardian works too, but it's far from as good as Aftershock for Thresh, as it only has synergy with Dark Passage.

I see Font of Life as the best rune to go here. You have so much CC on Thresh so you will be utilizing this rune most of the three in this slot. But Demolish can be very good, if you're in a winning lane and/or strong pushing team. Probably not the best of out the three runes, but it's far from bad. If used correctly. Unflinching gives you tenacity, but only when you use your summoner spells. So it's... Meh.

The next slot is relying a little bit more on the enemy team comp. Most of the time you go Conditioning because it gives you both armor and mr. Iron Skin can be picked against full AD comps and Mirror Shell against heavy AP comps.

Overgrowth is probably the best rune in the last slot. You basicly get max health scaled by your ADC farming. Second Wind is a good pick if you play in a losing lane as it give back some health after taking damage from enemies.

Secondary path: Domination

I like Cheap Shot a lot with Thresh. Not that you really need the extra damage, but you have so much CC in your kit. And the CD in on 4 seconds, so you can utilize it everytime you have your Death Sentence, Flay and The Box. And why not make some extra kill pressure? Zombie Ward is one of my favorite runes overall. You basicly have your wards giving vision for 3 extra minutes. Which is a lot. You also convert enemy wards to your own zombie ward when you kill them. For supports like Thresh, Zombie Ward is superior over Ghost Poro as you most likely will hide in the bushes often. And you don't really need vision in the bushed you stand in.

Escapes
If you end up in a bad situation yourself, you might have a chance to get away in by casting to a jungle monster or creeps in lane

Exapmle:

Lantern block
W is good to get your allies out of trouble or in to fights. But it also works for blocking the path your enemies take

Example: