Mastering unholy runes
In the case of duel wield, even before stacking mastery, 2 howling blasts hit harder than an obliterate, and as such howling blast takes a far more prominent spot in our priority. Unfortunately, while both frost and death runes can be used for said howling blast, unholy runes cannot, often leaving us with 2 ugly green runes to get rid of before we can go back to spamming HB and FS.
There are three ways to get rid of unholy runes, let's see which is the best.
Death and decay: 50k dmg
Plague strike: 24k dmg + 100k (full duration diseases, 10k per 3 seconds)
Obliterate: 80k dmg +45% chance for free HB = 115k dmg
HB: 79k dmg
Obviously your best bet is double HBs whenever possible, but let's say you have 1 unholy and 1 frost/death, what should you do?
In order from best to worst:
Using plague strike and HB gives 203k dmg IF diseases are about to fall off
Using plague leech, plague strike and 2 howling blasts gives 182k dmg
Using DnD and HB gives 129k dmg
Using obliterate gives 115k dmg
Using plague strike and HB gives 103k dmg
Ignoring the unholy rune and just spending the frost/death on HB gives 79k dmg
While it's true you can use plague strike and howling blast at half disease duration and count the 50% refresh as 50k dmg, it prolongs the ability to fully refresh diseases via the top option for 15 seconds, and is therefore not a damage gain. If blood plague is not just about to fall off, count it as if it isn't refreshing at all.
So, if diseases are about to fall off, plauge leech is off cd, or dnd is off cd, use the above options to remove unholy runes, otherwise just use obliterate if you have to.