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Against most armies, the 2 fexes in the back lobbing venom cannon shots are very low priority when the walla of dakkafexi, HT's, and rending is rolling in. But some lists are more inclined to take out your long range anti-tank, and if you just have to buy defensive upgrades instead of more rending, I'd suggest taking that into consideration.

So who fears the Gunfexes most?
I think Necrons with 1-2 Monoliths are a good bet for going straight for the gunfex. +1 wound, 2+ save wins here for fizzling out destroyer and gauss shots.

Hammerhead heavy tau will shrug off your devourers and go straight for the gunfexes. 2+ save is amazing vs. Ionheads, missile pods, seekers, and pulse weaponry. +1T will provide a greater benefit only against the 24" Plasma rifles and 12" Meltaguns. I'd go for +1 wound, 2+ save here. It's unlikely that most tau will be within 24" of your gunfex unless you've already lost.

TriFalcon only fears your shootiness, and may go for your gunfexes first as they are slightly harder to avoid than the devourer spam. +1T will provide some benefit against the pulse laser, starcannon (who takes these?) and scatterlaser fire. +1 wound, +1T probably provides the best benefit against standard kit falcon fire.

Heavy exorcist sisters will go for your gunfexes first. +1 Wound and +1 T is the only thing that will help, albeit marginally.

Any others?

Personally:

I buy every defensive upgrade there is on my two gunfexes. Including regeneration. Why? Because for the points I could get another 30 gaunts or so, and I just don't like playing with that many dudes. All my other useful slots are filled up already.

The actual strategic reasons are that some of the most common armies these days are vehicle-based. The things that give me the biggest fits are skimmer armies (Tau and Eldar and Dark Eldar) and the most reliable thing I have at killing these is the gunfexes (because most people choose not to get their skimmers within 18" of my dakkafexes).

Further, having a ton of points in two big ass hard to kill guys sitting in the back can be a big edge in objective based games. Instead of having 4 more 40pt gaunt squads that're suicidal, I have 10 wounds of T7 2+ save regenerating creatures that never get closer than 30".

Maybe not statistically the best way to play, and when I drop to 1500 all the upgrades come off, but it works great for me. And it'll just keep getting better as they take more heavy weapons out of more armies. Hurr.