Been giving some thought to making a new run using a character themed around being a mage killer/assassin. So far I'm looking at a Breton with the Atronach sign. My question is which to focus on building up first, Absorb (limited to in-game drop/reward items) or Resist (which I can craft otherwise I'd need to get drop/rewards).

Sounds like you're looking for immunity to magic and you like Bretons. If so, I'd go Breton + Mage birthsign. Getting the gear to boost magic resist from 50 to 100% is easier and requires less items than boosting spell absorption from 50 to 100%. You can put the extra slot or two in fortify magicka gear. Tons of blue juice that you regenerate with no worries and invincible to magic.

I think Atronach is a good way to pursue immunity to magic (if that is what you want) for non Bretons. Bretons are just naturally too cool right out of the box to worry 'bout Atronach.

I agree with Acadian. With a Breton in the unmodded game you can get 100% Resist Magic fairly easily (mods like OOO make that a bit more difficult).

For other races, Altmer's in particular, Atronach is great. But Bretons and a Mundane Ring can just shrug off magic attacks.

If you do take Atronach with a Breton or otherwise, I recommend focusing on Absorb. Remember you can increase Absorb Magic percentages with more than equipment. There are spells an potions to absorb magic attacks. But of course if you get to 100% Absorb, then the Breton's great Resist Magic ability is worthless.

I would go with a Bosmer, which is more RP I think, and you get the alchemy boost. Any class is OP with a silence potion, but a thiefy one might be able to tip toe around some of those nasty necro groups and snipe them down