With 0 games to actually back this up, just going off theory --
Starting Item: Talismen is generally better for anyone with AoE. IIRC the health regen counts per target so I believe he'd get better mileage out of it. First camp might be rough, would need a leash, but once you get both Q & E should be smooth sailing.
Smite Item: Well, Morde needs to stick to his targets, so I'd say Blue since he has 0 CC. Exception would be if you had a lot of CC on your team, then maybe Red if you're planning on running a more AD or on-hit build.
Enchant: Depends on build. Despite Morde's HP scaling on his passive he seems to perform better with AP, so probably Runeglaive Runic Echoes. If you are gonna try for tankier build than Cinderhulk, but I don't think he tend to be effective when build towards tank. I think Devourers would be kind of a gimmick/troll build, potentially entertaining in normals but not particularly viable.
Runes/Masteries are largely personal taste, but Keystones are where its at anyway.
Might be worth trying a CDR-oriented AP build, run the +5% CDR with Thunderlords Keystone. More CDR, more spells, more shield.
If going for an off-tank build I'd probably go with the Strength of Ages or whatever its called, defensive mastery where you steal %hp on a hit.