Mephisto is by far the most popular Diablo 2 Boss to farm with very good reason, as he is able to drop most items and has a very high chance of dropping valuable sets or uniques. Another attractive quality about him is that you can get to him fairly fast, so a whole run does not take longer than a minute.
Most holy grail items, like Harlequin Crest Shako, Mara’s Kaleidoscope, Highlord’s Wrath, Tal’s set items, IK set items, War Traveler, Gore Rider, Waterwalk, Titan’s Revenge, Wizardspike, Herald of Zakarum, Skin of the Vipermagi, Stormshield, Arachnid Mesh and plenty more has the highest chance to drop from Mephisto. He also has a high chance to drop high runes like Ber, Jah or Cham, the only exception being Zod.
As he resides in Durance of Hate level 3, the nearest waypoint is Durance of Hate Level 2. Unfortunately the map layouts can not be memorised, but your best bet will be to start searching for the Level 3 entrance by teleporting clockwise.
Having the teleport skill for farming is an absolute necessity. If you don’t play a sorceress, or have an enigma runeword that grants you the teleport skill, you should get an Ondal’s Wisdom set staff that provides 69 teleport charges, or a magic amulet that also provides teleport charges. By teleporting, you will get to Mephisto up to 3-4 times faster compared to running to him.
Since most of a Meph run consists of teleporting, the obvious build of choice is the build that can teleport the fastest. The Lightning Sorc is the only one capable of reaching 7 frame teleport casting rate at 200% faster cast rate, making it the build with by far the fastest movement speed.
The insanely fast teleporting is just one of the advantages of a Lightning sorc. By casting the Static Field skill once you are at Mephisto, you can reduce his life by 50% within 2 seconds, and then kill him with Lightning. The whole killing process takes no longer than 10 seconds. Another benefit of the lightning sorc is that it can deal a huge amount of damage while also having a high magic find %. You can wear magic find gear, have magic find charms in your inventory, and/or have a 6*Ist sword and a 4*Perfect Topaz Monarch as switch weapon set and switch for the kill. With a high magic find, you will often experience the excitement of finding 2, 3 or even 4 Unique or Set items at the same time.
Conclusion: My opinion is that the best strategy to start a ladder season is by creating a Lightning Sorceress and farming Mephisto firstly to find gear for yourself, then to sell your found items for runes and quickly get your desired runewords. Items dropped by Mephisto are amongst the most valuable ones throughout the first month of a ladder season, and he clearly has the highest return on investment on your time.