Yes, there is always a difference. Whether you feel the difference on an incredibly good connection is largely based off your skill. If you don't need frame perfect timing for something, it's not really an issue. There's also those who memorize buttons, and those who look at the screen and take visual cues on when to time things. I am the later, so I cannot play online. As starting at frame 0, I'll use an attack. The attack may show at frame 5. I need to input the next button at frame 3, but I only saw the attack at frame 5 instead of frame 3. So I input the next command at frame 8. This is WAY too late to enter the command, and I fail. Then, this occurs for everybody. There's lag in seeing your opponent and reacting. My opponent does an attack at frame 0. I see it at frame 5. It hits at frame 4. When I see it at frame 5, I react to block it. I press the guard button, but I've already been hit before I've even had a chance to block it.
I'm using very low numbers that aren't significant enough to matter, but just increase them and they can be very annoying. The point where there's 10 ms of lag is the point where it becomes noticeable if you're really good at the game. That is ONLY 6 frames. 6 frames DOES make a difference in fighting games. If you can play someone over the internet with less than 10 ms of lag, then is the only time it doesn't make a difference.