In order to achieve a perfectly optimized game, you absolutely must use the community's memory workarounds that pretty much every website mentions. The memory utilities and proper patches and plugins will give you a solid foundation to build on.
The Unofficial Skyrim Patch(es):
First and foremost, to start from a solid foundation you'll want to patch Skyrim. The game patched up to the latest version with no other mods installed can still cause problems and has many bugs--a common issue with Elder Scrolls games since they are so massive. These patches are installed the same way as a regular "mod", but they repair multiple known problems.
The main patches that you have probably already heard of are the Unofficial Skyrim Patches (known as "UKSP"). The UKSP is a ton (thousands and thousands and thousands) of adjustments/fixes to the game. Most well known modders always suggest using them. The latest (as well as the unofficial DLC patches) may be found on the Nexus here.
NOTE: The above UKSP patches are no longer online, and have been replaced / superceded by the USLEEP patches.
Script Fixes by Steve40:
As a supplement to the above patch(es) you may consider using the following script fix to help prevent papyrus log spam. If you don't know what that is, the summary is this: Papyrus is the script engine that Skyrim uses. It can get spammed with scripts which can lead to instability in game play such as freezing and crashing. The vanilla game (no mods installed) does have a few scripts that are known to cause some unhealthy log spam. This file is a replacement script that will fix those nasty critters:
> The LvlPredatorScriptFix(v2.2). *NOTE: The patch was lost when our prior host shut down. The below link may offter it though.
For more information about this script fix (for advanced modders who'll understand the weird jargon) you may wish to visit here. In summary, the USKP applies a fix of their own which only works on vanilla game creatures, but not on mod-added creatures.
NOTE: To install, it is recommend to use a mod manager. Place the "script" folder inside your Skyrim's data folder and overwrite any files (BACKUP the originals first, or use a mod manager like we suggested). As a final note, for those that don't really understand this, just stick with the official patches fix. If you know what to look for, and see that even with those you still have a problem, then consider adding in steve40's fixes.
SKSE (Skrim Script Extender):
The SKSE Plugin is (possibly) the most important plugin one can add to his game. It enhances scripting for Skyrim by allowing various work arounds which allows mod authors to do more with their mods. Suffice it to say, many mods require the SKSE plugin in order to work properly. Further, SKSE comes with the most important memory enhancing plugin built in--Sheshon's Memory Patch, (see "Memory Management" below) and makes it super easy to activate. Go ahead and add it in if you haven't already to elevate your modding experience to new heights.
> Download the latest version from here
Crash Fixes:
One of the latest and greatest aids in combating crashes is a wonderful plugin created by meh321. It enhances SKSE and older versions of memory patches and many users swear by his fixes. Further, on his Nexus page, he gives even more recommendations for INI alterations. All in all, his plugin and Nexus page are great resources for fighting against crashes.
> Download CrashFixes from the Nexus
SkyUI:
This plugin (/mod) recreates the horrible console menu making it PC friendly. It eliminates the need to scroll through a million items just to find one. It will instead open a single window full of information that a mouse user can easily utilize. Plus, again, many mods require SkyUI so that they can take advantage of its unique mod menu system. If you plan on playing Skyrim on a PC--and we're assuming you are since you are on this site, you will most definitely want this.
> Download SkyUI from the Nexus
NOTE: SkyUI requires SKSE to work properly.
Sheshon's Memory Patch:
The most major breakthrough in stabilizing Skyrim comes from the now famous "Memory Patch". A wonderful and genius utility that works around the limits that Bethesda has left us with (thanks Bethesda). This patch will undoubtedly aid greatly in stabilizing your game and virtually eliminate any CTDs, crashing, and or freezing.
Sounds good doesn't it? Click here to go to our page that will guide you in installing the patch. It'll help you, don't question our collective superior intellect.
NOTE: Utilizing the above memory plugin renders previous management utilizes such as Safety Load obsolete.
ENBoost:
The ENBoost is a memory management plugin that works ALONG WITH Sheshon's memory patch and in order to have a truly optimized game, you should use both together, as well as setup both properly for your system. That is where Sheshon's memory patch has the advantage--it is super easy to setup. ENBoost is a rather different type of beast and does require some serious tweaking to get right. You'll need to read up on it and make a few minute adjustments at a time until you feel that everything is working properly.
NOTICE: It is recommended that only users who are more familiar with computer use as well as modding attempt to use it. Further, if using a laptop, it could possibly hinder the game rather than help it (not proven, but not unproven either).
NPC AI "More Brains" plugin:
Our own team has developed a mod/plugin that enables Skyrim to handle a higher count of AI packages at once. Some people have reported dead AI bugs (NPC actors standing around being dumb rather than interacting with their environment or battling when suppose to be) when using mods that increase encounters. (Not all have reported the issue, but some have, and that was enough.) So, in order to counter that, we created Artificial Intelligence Limit Increaser. The best part is that you don't need to use up an esp slot. We supply the instructions right on the Nexus description page for the fix to apply it yourself. For those that don't feel comfortable making the edits, we have supplied a "mod" that does everything for you.
NOTICE: Great news! If you use our mod, The Sands of Time, the fixes are automatically applied for you. No need to make the additional tweaks or use the Artificial Intelligence Limit Increaser. You're welcome.
CleanMem:
This program would also fit under our "3rd Party" program section (see next chapter), but it seemed like the most appropriate place was here. CleanMem is a free program (a more advanced paid version is also available) that runs in the background and constantly cleans memory clutter while Skyrim is running. That way, Skyrim always has the most memory resources available as possible to do whatever it is trying to do.
Also, CrushBoss suggests cleaning the memory out before launching Skyrim (which you would of known if you read his guide you impatient jerk), and this program does that too. Indeed, it is a convenient little program that we recommend in order to fully optimize your game. In order to set it up to work with Skyrim properly you should watch this video (which comes straight from Grandbulwark's Skyrim Project Stability guide): Cleanmem Set Up.
Now that you have a good foundation to start from, continue forward to Chapter III: 3rd Party Software, to manage your mod loads better.