Theme, artstyle etc. doesn't really matter.
Of course, you should know your tools...
But think about some important points first:
* Story, joke-a-day, or what shall it be ?
* Sketching out a rough storyline/list of jokes ahead of time would be good (say, enough for a first season/book)
* Also: background infos, like worldmap, history, motivation of chars etc.
* Schedule, e.g. once or twice a week - pick something you can sustain in the long run.
* Also: buffer - slipping schedule is one sure way to annoy readers.
* Where to publish/store pictures?
* Do you have (at least an idea for) a basic layout for a website with About/Cast/Archive etc. ?