Depends to a large extent on what it is....the liquid metal stuff would be a real big problem, AS5 is an issue as .... well just read what the As5 folks say about it
Arctic Silver 5 was formulated to conduct heat, not electricity.
(While much safer than electrically conductive silver and copper greases, Arctic Silver 5 should be kept away from electrical traces, pins, and leads. While it is not electrically conductive, the compound is very slightly capacitive and could potentially cause problems if it bridges two close-proximity electrical paths.)
So, if this is a concern, I'd remove the cooler and CPU and clean both throrouhly as well as any areas affected if spilled over on MoBo...... If ua in no rush, the best stuff to use is
Indigo Xtreme Clean Non-Conductive Thermal Surface Cleaner - 30mL (XC-01)
http://www.frozencpu.com/products/13256/thr-106/Indigo_Xtreme_Clean_Non-Conductive_Thermal_Surface_Cleaner_-_30mL_XC-01.html
Indigo Xtreme Clean™ works better than other products. It possesses higher solvating power than isopropyl alcohol and emulsifying cleaners, yet leaves no residue. Unlike acetone, xylene, and toluene, Indigo Xtreme Clean is non-flammable and is safe for most surfaces.
Indigo Xtreme Clean is easy to use. Simply place a small amount on a clean, dry cloth, wipe the surface clean. One and done - no fussy two-step process. The surface will be left completely free of any thermal grease or stray material and ready to accept a superior thermal solution such as Indigo Xtreme™.
If in a rush, you could "get away with" 99% isopropyl alcohol but that does leave a residue. I do sometimes use the alcohol in step 1 to get off large amounts of "baked on grease" on metal surfaces then finish with the Indigo as a final clean in step 2. I'd don't use alcohol on PCBs tho; if TIM spilled or dripped on any circuitry, I only use the Indigo.
For what ya pay for an ounce of the Indigo stuff, you will get 16 ounces of alcohol, but having used both, I much prefer the Indigo..... my 1 ounce bottle is about 3/4 full after cleaning 6 GFX cards and 5 - 6 CPUs / coolers. I apply with Q-tips.
As for the line up thing, the "trick" is to make sure you are using the correct mounting bracket. Most aftermarket coolers come with several choices..... and typically will have 2 or 3 alternative holes to insert screws through. And if you are confused reading thr directions, they all "make sense" the 2nd time you install it but I think the staff writing the directions and preparing the diagrams challenge each other to see how confusing they can make it for 1st time users.