Each Rune has a specific task that needs to be completed (i.e.: Ammo Boost - Pick up 500 weapon items). If you are following a guide and have all of the Runes up to and including Mission 7 (Argent Facility Destroyed) you can restart a check point to clear all of the runes and a few of the Masteries. The 7th Rune prior to this point is In-flight Mobility.
You will reach a checkpoint that will have a Gauss Cannon and a Datalog directly in front of you after going through a door. There will also be a Hologram in the same room on the left wall. In this area there is a Gore Nest, about 5 possessed, a 'flaming' possessed (Cannot recall the name), a Hell Razer, and a Shielded Security possessed. Pick up the Gauss (if you didn't already have it), snipe the Hell Razer coming down the steps in the back, and then snipe the Security Possessed either just before or after he jumps down from the lest side so he won't have his shield up, then it's easy pickings on the fodder. Clear the room - even the 3 on the opposite side if you really want to, then either restart the check point or jump onto the purple electric floor to kill yourself. Be sure to not active the Gore Nest until after you have everything upgraded so you do not lose the checkpoint.
In this area I finished all of my current Runes except for Ammo Boost; I also mastered the Pistol, Super Shotgun, and Gauss Cannon Siege Mode. This spot clears the hardest ones imo as there are 3 that deal with Glory Kills and the Possessed are easy targets. After this the rest of the runes are easy to clear - only exception being the final Rune Saving Throw. I have only just gotten to this on and obtaining it is challenging. You get 1 health point and a Gauss Cannon in Siege mode to clear 9 demons.
EDIT: The Saving Throw is easily upgraded as well. After you acquire it and you continue on in the mission (Lazarus), you will follow a walkway and drop into a circular room. A door will open to a hallway with a portal at the end which will put you into a battle with a bunch of demons. With Saving Throw active you basically just need to let them 'almost' kill you. Just before you would die everything will go slow motion then blast with the BFG and wipe out the demons; then just rinse and repeat. Kill 10 of them in that slow mode and it will upgrade. If you get hit during the slow mode you will die and have to try again. Be sure to restart your check point after the upgrade you so get all of your ammo back, as after that battle you go against the 2-phase Cyber-Demon fight! So be sure to abuse the Riches rune to kill off everything while not spending ammo.
Hope this helps!