Hide unnecessary buttons
Practically everything I use is hotkeyed. The only primary buttons I show are spells with a range or cooldown. My buttons are set up to turn red when out of range (Bartender) and display a cooldown time. (OmniCC) Thus, I don't need spells like arcane explosion or flamestrike on my bar. I also use only 1 button for shared ranges or cooldowns, such as only showing fire ward instead of both fire ward and frost ward. I also have a tiny, out-of-the-way secondary bar for common tasks like food and portals. Gems and potions I just open my bag for. It's not that much trouble, but a macro for using them would also be useful.
Maximize readability
The best way to increase readability is to reduce clutter and strategically place your frames. Important stuff should be near the middle of the screen. The developers of Bigwigs figured this out and implemented a way for incoming timers to pop into the middle of the screen. Blizzard apparently hasn't, though, and put their unit frames way up in the corner of the screen. Get some unit frames like Pitbull and move that to the center of the screen, or even use a HUD. If you're a healer, it would be wise to have raid frames somewhere close as well.
Another potential readability block I have found is error text. By error text, I mean the stuff you get from spamming spells or trying to take a portal while mounted. After starting from scratch on my UI a month ago, I realized how important ErrorMonster is. My BigWigs warning text and Blizzard's error text are basically in the same place. Eliminating error text makes it easier to read whatever crap BigWigs is trying to tell you.
Use "conditional" buttons and frames
There isn't as much room for this since patch 2.0, but it is still possible. I have a giant empty button for macros I need on certain encounters. This includes targeting Spitfire Totem, using Tainted Cores, or equipping/using Staff of Disintegration. Before a fight, I just drag that macro into that hidden button slot and bam, I'm ready to fight. I also have a focus frame for sheeping. Combined with a /focus-ing sheep macro. This frame is basically just a big 3D portrait to monitor the status of my sheep.
Avoid obstructing your view
<p>There are mods out there that intentionally do this and I have no idea why. Putting a giant frame behind huge blocks of addons does absolutely nothing. It doesn't even look good. If there is little margin, fine, but often addon package authors will overdo framing. Viewport modifiers are another horrible idea. Why INTENTIONALLY reduce your visibility? Having your game look "cinematic" benefits nothing. Unless one of those viewport mods increases your horizontal field of vision, you are simply losing visibility. Photek was famous for this back in the day. (the package looks like it has gotten much more sensible since) It looked pretty when you zoomed in, but overall the loss wasn't worth it.
edit: Since changing blog software, I have lost the screenshots for my old interface. Sorry.
Practically everything I use is hotkeyed. The only primary buttons I show are spells with a range or cooldown. My buttons are set up to turn red when out of range (Bartender) and display a cooldown time. (OmniCC) Thus, I don't need spells like arcane explosion or flamestrike on my bar. I also use only 1 button for shared ranges or cooldowns, such as only showing fire ward instead of both fire ward and frost ward. I also have a tiny, out-of-the-way secondary bar for common tasks like food and portals. Gems and potions I just open my bag for. It's not that much trouble, but a macro for using them would also be useful.
Maximize readability
The best way to increase readability is to reduce clutter and strategically place your frames. Important stuff should be near the middle of the screen. The developers of Bigwigs figured this out and implemented a way for incoming timers to pop into the middle of the screen. Blizzard apparently hasn't, though, and put their unit frames way up in the corner of the screen. Get some unit frames like Pitbull and move that to the center of the screen, or even use a HUD. If you're a healer, it would be wise to have raid frames somewhere close as well.
Another potential readability block I have found is error text. By error text, I mean the stuff you get from spamming spells or trying to take a portal while mounted. After starting from scratch on my UI a month ago, I realized how important ErrorMonster is. My BigWigs warning text and Blizzard's error text are basically in the same place. Eliminating error text makes it easier to read whatever crap BigWigs is trying to tell you.
Use "conditional" buttons and frames
There isn't as much room for this since patch 2.0, but it is still possible. I have a giant empty button for macros I need on certain encounters. This includes targeting Spitfire Totem, using Tainted Cores, or equipping/using Staff of Disintegration. Before a fight, I just drag that macro into that hidden button slot and bam, I'm ready to fight. I also have a focus frame for sheeping. Combined with a /focus-ing sheep macro. This frame is basically just a big 3D portrait to monitor the status of my sheep.
Avoid obstructing your view
<p>There are mods out there that intentionally do this and I have no idea why. Putting a giant frame behind huge blocks of addons does absolutely nothing. It doesn't even look good. If there is little margin, fine, but often addon package authors will overdo framing. Viewport modifiers are another horrible idea. Why INTENTIONALLY reduce your visibility? Having your game look "cinematic" benefits nothing. Unless one of those viewport mods increases your horizontal field of vision, you are simply losing visibility. Photek was famous for this back in the day. (the package looks like it has gotten much more sensible since) It looked pretty when you zoomed in, but overall the loss wasn't worth it.
edit: Since changing blog software, I have lost the screenshots for my old interface. Sorry.
I use xperl, dominos, and titan bar to customize my wow interface. The I use the settings to make everything really small so I can maximize visibility. I was weary of addons at first. Then I tried some and was amazed at how much they can improve gameplay.