So how is "Sforno" - ספורנו as in רבי עובדיה ספורנו - actually pronounced? In 2008 Dikdukian noted that he "must have heard five different pronunciations of that name over the years: Siforno, Siporno, Sipurno, Sforno, etc."
I don't have a definitive answer, and my research is tentative. But here are some points to consider. First, it seems to me that the confusion stems from the fact that on the one hand this obviously is not Hebrew, but on the other, we only see his name spelled in Hebrew (except not really, as we shall see). In Hebrew a word cannot begin with a consonant cluster - that is, a word like "stop" can't really exist; it would have to be pronounced "s'top" or something like that. Thus if you would treat ספורנו as a Hebrew word it could neither be "Sporno" or "Sforno." It would have to be "S'porno" or "S'forno" (I would generally prefer to spell that with an "e", like "Seforno"). Secondly, this first consonant, a mobile sheva also will change the hard /p/ to a soft /ph/ or /f/. Thus, once again, treating the name as Hebrew it could really only be "Seforno." But again, it is not Hebrew.
Although it seems that the origin of the name must be some Italian town or city, I have been unable to locate this place. But we can see that it is a place by the title page of a book written by him and published in 1537, while he was still very much alive. His name is given (incorrectly) as עובדיה מספורנו, Ovadyah of ספורנו. Thus it is clear that it is a place, for a contemporary of his (perhaps his publisher) assumed that this was the proper form of his surname. In the text itself, the book begins נאם הצעיר עובדיה בכמה"ר יעקב ספורנו ז"להה מתושבי בולוני"יא. And no, I did not copy it exactly correctly. I was not able to read the letters he gives after his own name. Feel free to have a look and interpret them. See it here or here and let me know.
So what can we do besides this? We can look if or how his name is written in the Latin alphabet. In Christian sources his name is often given as "Abdias Sporno," but also "Sphorno" and "Sporno." And others besides (Siporno, etc.). So this is not incredibly helpful, especially as they are later (at least the ones I've seen).
However, there are at least two highly significant sources. The first is the actual Latin text of his medical diploma, which was published in the journal Rassegna Mensile di Israel in 1962. However, I only saw it cited, but I didn't see it.
The second may be even more significant, because it likely reflects the actual pronunciation used by the man himself. Johann Reuchlin - who was taught Hebrew by R. Ovadya Sforno - writes the following "Abdia filio Jacobi Sphurno" (Johann Reuchlins Briefwechsel p. 92). This letter is dated 1506, when the man in question was still only 30 or 31 years old, very much alive, with nearly 45 years left to go. Reuchlin knew him personally. So perhaps we should say that Sfurno (to use a more modern English spelling) wins. Not S'furno, not Sporno, and not even Sforno. Of course we also note that Reuchlin also Latinized Ovadiah as well as Jacob in this letter, so perhaps he somehow did the same to the surname as well. Furthermore, we also have to be sure how this deceptive word is pronounced. We must bear in mind that the pronunciation of Latin vowels by a German man in 1506 may not match our idea of how these vowels should sound.
Another line of evidence should be considered, which is that the Sforno family was very real and persisted for many generations, perhaps into recent times or even today, hopefully. So it is possible that there is a living tradition within this family of how to pronounce the name, and maybe it is "Sporno." That said, consider the Abarbanels, who have people who pronounce it Abarbanel and Abravanel (and other pronunciations besides). So family traditions aren't necessarily so strong or authoritative I know, for example, that some last names were pronounced one way in the old country, but Americanized (or Anglicized, or Israelized or Canadized, etc.) . There are countless examples. Shterns became Stern, Shapiras became ShapirO, and many more like it. If any particular person is unaware of how their own name's pronunciation was changed, than what good would their conviction about how it is pronounced be? Not very. Similarly, if there is a living tradition from descendents of this family of how Sforno was pronounced, then that should be noted, but not necessarily regarded as authoritative.
As for the origin itself, surely that will shed light. Maybe an intrepid Google Mapper can enlighten us. In the meantime, in light of Reuchlin, I would put my money with Sforno over Sporno or Seforno, but perhaps even Sphurno is really best of all.