Keystone Rune

Phase Rush speeds Vladimir up and provides him with slow resistance for 3 seconds after the major burst combo ( Tides of Blood -> Flash -> Hemoplague -> Transfusion -> Sanguine Pool) and helps in chasing down the enemy and/or dodging skillshots

Second Line Rune Options

• Nimbus Cloak Speeds Vladimir up by a lot if his ultimate Hemoplague is used in a combo
• Nullifying Orb is an option in burst AP lane matchups and against enemy AP team compositions

Third Line Rune Options

The choice here depends on the in-game build

• Transcendence is most preferable because it provides Vladimir with high damage potential already in the mid game
• Celerity is a good option in a movement-speed orientied build because it then provides you with more AP
• Absolute Focus is a viable option in a AP-oriented build and Vladimir's burst combo hits even heavier if his HP is above 70%

Fourth Line Rune Options

• Scorch's damage helps Vladimir to play more aggressive in the laning phase (especially against melee opponents) but falls off in the later game
• Gathering Storm provides nothing in the early game but starts to kicks-in after 20 minutes with increased damage in every spell-cast and helps in carrying the game

• Cosmic Insight provides Vladimir with 5% CDR for all spells (including summoner spells and active items) and is a must have (together with Ionian Boots)
• Perfect Timing is viable again since Stopwatch can now be used after 8 (instead of 10) minutes
• Depending on playstyle Magical Footwear, Future's Market, Minion Dematerializer and Biscuit Delivery are also viable options

The following Domination runes can provide more stacking AP, self-healing, more vision control, bonus true damage or less ultimate cooldown:

• Cheap Shot
• Taste of Blood
• Zombie Ward
• Ghost Poro
• Eyeball Collection
• Ravenous Hunter
• Ingenious Hunter
• Relentless Hunter
• Ultimate Hunter

Choosing runes from the Resolve tree as secondary runes provide more tankiness. Viable options are:

• Demolish
• Bone Plating
• Second Wind
• Chrysalis
• Overgrowth
• Unflinching
• Revitalize