On my heavily modded game I think I accidentally screwed some stuff up. When playing around with options like deadly reflex, immersive first person view, and bbb, trying to figure out what skeleton config and related mods I wanted, the game stopped working. It crashed when I loaded a save or tried to make a new character, without an error message. Just bam, desktop.
That made sense to me, I was messing with the skeletons that were incompatible with deadly reflex, which was my currently used skeleton replacing mod.
The problem I have is when I switch back to deadly reflex, or remove it completely, or try any other skeleton mods, the game crashes like described above.
It took 20+ hours, lots of caffeine, multiple new game vanilla installs, and immeasurable patience and frustration troubleshooting this crash back to the skeleton. So I'm pretty sure its one of the mods above. So ultimately I found, by making a fresh install with just deadly reflex and enabling/deleting the archive invalidation, that the problem boils down to data/meshes/characters/_firstperson/skeleton.nif.

Even with a brand new install, my computer seems now permanently incompatible with any mod that adds the first person skeleton.nif to the data (so only the vanilla one works). This is a phenomenon I have never seen in my 5+ years of modding.

I used to play with deadly reflex just fine. What happened? Why can't even a fresh install read a fresh skeleton.nif without crashing when I was able to use deadly reflex's skeleton.nif even with multiple other mods?
That my computer itself seems permanently intolerant of an oblivion mod's .nif file when its worked before defies all logic I have about how these elder scrolls games work. So I really need some help if I ever want to play this game again!

I'm no expert but your description does not help me or anyone else for that matter to help you. We need to know what mods you are currently using and what other utilities are being used. What are your system OS? Where did you install your game? Are you using Wrye Bash and BOSS to manage and sort your mods?

I use obmm,wrye bash,obse,game is and always has been installed on an external drive. The only mod I am now trying to use is deadly reflex. The problem is that oblivion won't play when there's a custom skeleton.nif in the 1st person meshes. It doesn't matter if there are other mods checked or if I'm just trying to use oblivion. I've confirmed with archive invalidation that the problem isn't with load order or an esp, its literally "any customized 1st person skeleton.nif." I am wondering why the presence of this file breaks the game even when no mods are loaded.

Have you done a fresh install?

Here's the latest thread regarding deadly reflex 6. http://www.gamesas.com/topic/1219866-relz-deadly-reflex-6-beta-the-official-release-and-bug-report-thread-5/ The mod seems to be quite buggy from the looks of it though functional. Maybe you can find the answers there.

A skeleton file crashing the game is very unlikely but not unheard of. To stay with the truth, every item you equip can crash the game when there's trouble with its rigging, as can every animation played, when it attempts to move bones not present.

To me your issue sounds like a conflict of some kind. And yes, changes to resource files can do these things even without an ESP or ESM ever loaded.