If you lined them all up in their prime, with today's equipment, on today's court, and played a round-robin tournanment, Serena would win it. But I don't think that's what you meant.
Helen Wills Moody made the finals, in singles, of every slam she ever played, except for a couple defaults. That and 19 slam wins is a pretty good argument. (She never played OZ, so no chance of a Grand Slam.)
She's probably the best of the grass court era, though Court obviously has a good argument. In the hard court era, Graf has no real equal.
We'll never know what Althea Gibson's career would have been, she was excluded from so many tournaments. Like Connolly and Seles, you can only speculate.
When comparing the Williams sisters with the players of the 1990's, the key match for me was Steffi Graf v Venus Williams in the quarter finals at Wimbledon in 1999, a match that Graf won 6-2 3-6 6-4. This was just 1 year before Venus won her first Wimbledon. Graf had only recently returned to the circuit after long standing knee and back problems. Moreover, as Graf went through that Tournament, it became evident that her knee problems had resurfaced, a fact that led her to withdraw from the mixed doubles (in which she was competing with John McEnroe) to protect the injury in advance of the singles final against Davenport. However, in the final it was pretty evident that the knee injury was impeding her and she lost. She retired a month later. Nevertheless, her quarter final performance against Venus illustrated that had Graf been born 10 years later, she would still have been the dominant singles player despite the presence of the Williams sisters. It is also worth noting that on the Williams sisters best surface, grass, they very much benefitted from the fact that during the zero's there was a distinct lack of quality grass court players. An illustration of this is that when Venus won Wimbledon for the first time in 2000, she met Martina Hingis in the quarter finals. Grass was Hingis's least favourate surface (being knocked out of Wimbledon twice in the first round) and by 2000, she was starting to have problems with her ankles (which would ultimately lead to her first retirement). However, despite all this, Hingis almost won that match (giving Venus her toughest match of the tournament), Venus winning 6-3 4-6 6-4. Had Hingis won, she almost certainly would have gone on to win her second Wimbledon.
Further illustrations of the Williams sisters vulnerability on there favourate surface are:-
* Justine Henin was by far the best clay court and (jointly with Kim Clijsters) hard court player of the last 10 years. Henin's multiple victories against the sisters at the French and her demolition of both sisters at the 2007 US Open is testament to that, as was Clijsters victory over both sisters at the 2009 US Open just weeks after her come back from retirement. Hence, the Williams sisters only dominated on grass and had there been no Wimbledon, Henin would have gone down without any doubt whatsoever as the greatest player of her generation.
* Sharapova had the potential to be a really great grass court player. However, she has been hampered by injuries. Consequently, she has only really performed to her full potential once at Wimbledon - in 2004 (ok, she got to the final in 2011 but with that shoulder problem - for me she is only a shadow of the player she was back in 2004). Her performance in annihilating Serena in the 2004 final for me highlighted the fact that when the sisters came up against a quality grass court player, they had no answer. That is, had they come up against players like Graf and Navratilova at their peak, they would have come off second best every time. Hence, the reason for their dominance on grass had much more to do with the fact that there was a dearth of grass court talent during the zero's. Moreover, Serena's defeat to Jill Craybas in the 2005 Wimbledon highlights that the sisters were even vulnerable to going out against players outside the top 32 and Venus's defeat to Jankovic at the 2006 Wimbledon shows that they were also susceptible to being knocked out by players who rarely performed well on grass (Jankovic having never got beyond the fourth round at Wimbledon). Furthermore, Elena Dementieva illustrated at the 2009 Wimbledon championships that when the sisters playing at their very best came up against a good player playing to their full potential, they were very beatable. In the 2009 semi, Elena had Serena match point down and was very unlucky to lose that match.