San Jose, on the other hand, does suck to get to from the East Bay. Best plan is to avoid going to the South Bay, or to hope that your destination is within striking distance of the Amtrak station. Or to hope that they finally finish the Bart connection. I agree that Caltrain gives you better South Bay access; I'd be tempted to Bart in to Millbrae and transfer to Caltrain if I still lived in the area and didn't feel like driving.
When I lived in the East Bay, I would end up in San Jose only 2-4 times per year, and I'd usually drive. On the other hand, I worked in San Francisco for over three years, and I never drove to the City once during that time; a mix of Bart and ferry trips (depending on where I lived at the time) handled my commute nicely.
There's also a great start-up incubator (or at least there was) in downtown Oakland; a start-up that I joined moved in there for a year or so, and that made for an even easier commute.
1. Do you live in the same place that the accelerator is -- in Downtown Oakland? Is that considered a safe neighborhood? You compare that with your founder commuting from North Beach, which is not a business district, so he likely lives there. North Beach is good neighborhood that lacks an underground lightrail but is otherwise a desirable neighborhood -- plenty of bars/restaurants, walkable from downtown, close to the bay, less crime, etc. I think it is unfair to compare commuting from Downtown<->Downtown with Community<->Downtown.
2. There are many commonly biked routes in SF that have no gradient, failing which, one can always walk, muni, or ride-share over to the destination. Owning a car is pretty unnecessary in SF (like it is in Oakland).
3. As someone who has done the BART + 181 journey more times than I wanted, in my experience it takes 1:30+ reach downtown San Jose from east bay. Which is kinda acceptable if your destination is in downtown San Jose. Even a few miles out (N 1st St., Cupertino, Mtv., or Sunnyvale) and you're in for a 2:30 + hour one way commute using the public transit. What I realized was that nothing beats a car in South Bay. Why do you say that San Jose is more easily accessible from Oakland than from SF when SF has a < 1 hr bullet Caltrain that reaches all South Bay cities' downtown?