I am going to list all of the .ini tweaks that I use in my game, with credits and links to the original posts/sites that i found them. Like so many other people, I spend more time modding and fine-tuning my game than actually playing it. What follows is a list of helpful tweaks, sorted by effect.

You can find your Skyrim.ini and SkyrimPrefs.ini in your Documents/My Games/Skyrim Folder. As a rule of thumb, its a great idea to back up these two ini files before editing them, so you can revert back if you cause any errors.

Also, if you change any options through the Skyrim Launcher after manually editing your ini files, your changes may be overwritten.

Performance:

Multi-Core CPUs - These tweaks increase the power of a multi-core rig by multi-threading processes

In Skyrim.ini Add/Edit:

[BackgroundLoad]
bBackgroundLoadLipFiles=1
bLoadBackgroundFaceGen=1
bUseMultiThreadedFaceGen=1
bBackgroundCellLoads=1
bLoadHelmetsInBackground=1
bUseMultiThreadedTrees=1
bUseBackgroundFileLoader=1

[Animation]
bMultiThreadBoneUpdate=1

[HAVOK]
iNumThreads=XX

[General]
bUseThreadedTempEffects=1
bUseThreadedParticleSystem=1
bMultiThreadMovement=1
bUseThreadedMorpher=1

[Decals]
bDecalMultithreaded=1

In SkyrimPrefs.ini Add/Edit:

[Navmesh]
bUseThreadedMeshes=1

[Trees]
bUseMultiThreadedTrees=1
bShadowMaskZPrePass=1

[BackgroundLoad]
bBackgroundLoadLipFiles=1
bLoadBackgroundFaceGen=1
bUseMultiThreadedFaceGen=1
bBackgroundCellLoads=1
bLoadHelmetsInBackground=1
bUseMultiThreadedTrees=1

[General]
bUseThreadedParticleSystem=1
bUseThreadedBlood=1
bUseThreadedMorpher=1
bUseThreadedTempEffects=1
bUseThreadedTextures=1
bUseThreadedMeshes=1
bUseThreadedLOD=1
bUseThreadedAI=1
bUseThreadedMorpher=1

[Decals]
bDecalMultithreaded=1

For "iNumThreads" ( the XX value above) set this to the number of CPU cores your PC has. If you have 4 or more leave this as 5 (maximum).

(source: Skyrim Tweak Guide 2.2)

Decreasing Script Lag - The scripting language used in Skyrim, Papyrus, is not the speediest of languages. Script queues can become lagged, and even halted, in a game using script-heavy mods. Using this tweak in my game even seemed to fix the lip synch problem that reared its ugly head again in the 1.9 update for Skyrim.

In Skyrim.ini add/edit:

[Papyrus]
fUpdateBudgetMS=800
fExtraTaskletBudgetMS=800
fPostLoadUpdateTimeMS=2000
iMinMemoryPageSize=256
iMaxMemoryPageSize=512
iMaxAllocatedMemoryBytes=2457600

(Source: Skyrim Script Lag)

Gameplay:

Better Aiming - These tweaks will help improve aim and range with bows and crossbows.

Add/edit in Skyrim.ini:

[Combat]
fMagnetismStrafeHeadingMult=0.0
fMagnetismLookingMult=0.0
f1PArrowTiltUpAngle=0.7
f3PArrowTiltUpAngle=0.7
f1PBoltTiltUpAngle=0.7
f3PBoltTiltUpAngle=0.7

[Actor]
fVisibleNavmeshMoveDist=12288.0000

(Source: Skyrim Archery Tweak)

Visuals:

Whether you have an Nvidia or ATI/AMD video card, the best resource for tweaking Skyrim's visuals is here. I couldn't improve on the content, or splice together a better guide from different sources. You will probably spend a lot of time fine-tuning these settings to balance performance and quality.