In the case of dual 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. (single target)
There are three ways to get rid of unholy runes, let's see which is the best.
Death and decay: 88.6k dmg
Plague strike:48.6k dmg + FP*2, 54k + disease, 22k per 3 seconds
Obliterate: 175k dmg + FP*2, 54k +45% chance for free HB, 117.6 = 292.6k dmg
HB: 261.4k *FP, 27k 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 leech, plague strike and 3 howling blasts gives 831.6k dmg
Using plague strike and HB gives 530k dmg IF diseases are about to fall off
Using DnD and HB gives 350k dmg
Using plague strike and HB gives 310k dmg
Using obliterate gives 292.6k dmg
Ignoring the unholy rune and just spending the frost/death on HB gives 261.4k dmg
While it's true you can use plague strike and howling blast at half disease duration and count the 50% refresh as 110k 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. This includes times when you use PL to take BP off early.
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.
Note: Due to DW's current state of being close to GCD locked most of the time, we need to reexamine the way to deal with unholy runes. While the above-mentioned list is accurate in terms of numbers, obliterate is more complicated than it seems. Obliterate has two possibilities, it either does 175k in one GCD, or 436k dmg in 2 GCDs. While we can average this out easily, as done above, the GCD cost has to be considered. Using DnD/HB or PS/HB does slightly more than obliterate on average, but costs 2 GCDs. Using obliterate over DnD is a gain if you are GCD capped. Depending on luck, you'll either gain free damage with the rime proc, or gain a GCD which will avoid overflowing resources which will be a damage gain. If you are not GCD capped, DnD/HB and PS/HB wins out.