hmm… Yojimbo… sounds strange…either u didnt do what i said…or else ur ET is fecked … j/k 
(also note, SOME variables cannot be set by a vid_restart only…)
How do you set your variables…?
- by exec’ing a setup file ?
- Edit the etconfig.cfg ?
or 3. set each variable through console ?
U got any mysterious vars going on :P? …try simple exmaple… like u mentioned the r_picmip…
well…what i would do… (to really break it down, maybe also some redundandt stuff… but again to be sure…just do it :D)
note: before u do this.,make a backup of your config… (if u like) oke…here goes
- Be sure to have a file, that contains all the changes u wanna add to your game (cvars, scripts). (ex “mysetup.cfg”)
- Open ET (no mod mode) , and write cvar_restart in console…and then QUIT et.
- Start ALL over… (meaning…delete ALL profile folders, and all etconfig.cfgs(also those in etmain))
- disable/remove any of the autoexec.cfg’s (for now, just so i know that things aint going on there)
- Open ET again …now you should have succeded to open a fresh new ET with pure default settings, make a profile and continue… setup the very basics, then quit ET and reopen.
- now…set a variable… DONT EXEC THE WHOLE SETUP YET …set variable r_picmip 3 by \seta r_picmip 3 (and press enter :P)
- close game entirely, quit…then restart, STILL in no-mod-mod…and see if it remembers the r_picmip 3 setting… if it does NOT… then i give up…
- IF it remembers…now try loading a mod…and see if the setting is transferred to the mod…
- close game…open AGAIN in no-mod-mode, exec your whole script,var stuff…and start doing what uve always done from there…thigs should be working from here…
if it suddently fucks up after uve loaded your complete setting…i would guess u have a bad setup…
and last…if u dont more or less do exactly what i write…i cant guarantee nothing 
if u still mean that this does not work…pm me, im sure we can work it out step by step over a chat…
(edit)
I may add… what really matters…is if ure running in a mod or not… if u delete the files metioned…and that u dont reuse your old etconfig.cfg as “setup”…
when i write “open ET”…i mean you doubleclicking the default EXE icon in game folder…(or non-modded shortcut)…NOT trough a game launcher (ASE/pathfinder)… duh
i know…but i have to be sure
(also for the noobs out there mayeb reading this post )